Methods for treating conditions and diseases

Abstract

Provided herein are dosing regimens and methods for treating conditions and diseases characterized by a reduced expression or function of NaV1.1 protein by modulating splicing of a pre-mRNA encoded by an SCN1A gene. The dosing regimens and methods can be used to treat Dravet Syndrome or other conditions and diseases.

Description

WSGR Docket No.47991-748.601 METHODS FOR TREATING CONDITIONS AND DISEASES CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 569,003, filed March22, 2024, U.S. Provisional Application No.63 / 691,797, filed September 6, 2024, U.S. Provisional Application No.63 / 728,013, filed December 4, 2024, and U.S. Provisional Application No.63 / 751,196, filed January 29, 2025, each of which applications is incorporated herein by reference in its entirety. BACKGROUND

[0002] Nervous system disorders are often associated with channelopathy, characterized by thedisturbed function of ion channels that mediate neuronal excitability, neuronal interactions, and brain functions at large. Mutations in the SCN1A gene, which is part of the SCN1A-SCN2A-SCN3A gene cluster that encodes alpha-pore forming subunits of the neuronal voltage gated sodium channel, can result in expression of NaV1.1 protein (also termed as “NaV1.1”) with reduced functions as compared to a wild- type NaV1.1 protein, reduced expression of NaV1.1, or both. Mutations in SCN1A gene are associated with development of a number of diseases and conditions, such as Dravet Syndrome (DS) (Miller, et al., 1993-2015, GeneReviews, Eds. Pagon RA, et al. Seattle (WA): University of Washington, Seattle, Bookshelf ID: NBK1318, and Mulley, et al., 2005, Hum. Mutat.25: 535-542). SUMMARY

[0003] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:WSGR Ref. No.: 47991-748.601 (I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and a first maintenance dose following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the first maintenance dose independently contains the compound at an amount of from about 25 to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, and the first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the second loading dose.

[0004] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and a first maintenance dose following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the first maintenance dose independently contains the compound at an amount of from about 25 to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, the third loading dose is administered from 2 weeks to 12 weeks after the second loading dose,WSGR Ref. No.: 47991-748.601 and the first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the third loading dose.

[0005] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; and administering to the human subject a first maintenance dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 169th day (±7 days) of treatment, (b) 4 months (±7 days) after the second loading dose, or (c) 16 weeks (±7 days) after the second loading dose.WSGR Ref. No.: 47991-748.601

[0006] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; administering to the human subject a third loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 85th day (±7 days) of treatment, (b) 1 month (±7 days) after the second loading dose, or (c) 4 weeks (±7 days) after the second loading dose; and administering to the human subject a first maintenance dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 197th day (±7 days) of treatment, (b) 4 months (±7 days) after the third loading dose, or (c) 16 weeks (±7 days) after the third loading dose.WSGR Ref. No.: 47991-748.601

[0007] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; and administering to the human subject a first maintenance dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 169th day (±7 days) of treatment, (b) 4 months (±7 days) after the second loading dose, or (c) 16 weeks (±7 days) after the second loading dose.WSGR Ref. No.: 47991-748.601

[0008] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; and administering to the human subject a first maintenance dose of about 45 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 169th day (±7 days) of treatment, (b) 4 months (±7 days) after the second loading dose, or (c) 16 weeks (±7 days) after the second loading dose.WSGR Ref. No.: 47991-748.601

[0009] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; administering to the human subject a third loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 85th day (±7 days) of treatment, (b) 1 month (±7 days) after the second loading dose, or (c) 4 weeks (±7 days) after the second loading dose; and administering to the human subject a first maintenance dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 197th day (±7 days) of treatment, (b) 4 months (±7 days) after the third loading dose, or (c) 16 weeks (±7 days) after the third loading dose.WSGR Ref. No.: 47991-748.601

[0010] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; administering to the human subject a third loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 113th day (±7 days) of treatment, (b) 2 months (±7 days) after the second loading dose, or (c) 8 weeks (±7 days) after the second loading dose; and administering to the human subject a first maintenance dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 225th day (±7 days) of treatment, (b) 4 months (±7 days) after the third loading dose, or (c) 16 weeks (±7 days) after the third loading dose.WSGR Ref. No.: 47991-748.601

[0011] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 85th day (±7 days) of treatment, (b) 1 month (±7 days) after the second loading dose, or (c) 4 weeks (±7 days) after the second loading dose; and administering to the human subject a first maintenance dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 197th day (±7 days) of treatment, (b) 4 months (±7 days) after the third loading dose, or (c) 16 weeks (±7 days) after the third loading dose.WSGR Ref. No.: 47991-748.601

[0012] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 85th day (±7 days) of treatment, (b) 1 month (±7 days) after the second loading dose, or (c) 4 weeks (±7 days) after the second loading dose; and administering to the human subject a first maintenance dose of about 45 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 197th day (±7 days) of treatment, (b) 4 months (±7 days) after the third loading dose, or (c) 16 weeks (±7 days) after the third loading dose.WSGR Ref. No.: 47991-748.601

[0013] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 113th day (±7 days) of treatment, (b) 2 months (±7 days) after the second loading dose, or (c) 8 weeks (±7 days) after the second loading dose; and administering to the human subject a first maintenance dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 225th day (±7 days) of treatment, (b) 4 months (±7 days) after the third loading dose, or (c) 16 weeks (±7 days) after the third loading dose.WSGR Ref. No.: 47991-748.601

[0014] Provided herein, in some aspects, is a dosing regimen for administering a compound according tothe following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day (±7 days) of treatment, (b) 2 months (±7 days) after the first loading dose, or (c) 8 weeks (±7 days) after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 113th day (±7 days) of treatment, (b) 2 months (±7 days) after the second loading dose, or (c) 8 weeks (±7 days) after the second loading dose; and administering to the human subject a first maintenance dose of about 45 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 225th day (±7 days) of treatment, (b) 4 months (±7 days) after the third loading dose, or (c) 16 weeks (±7 days) after the third loading dose.WSGR Ref. No.: 47991-748.601

[0015] In some embodiments, the dosing regimen further comprises administering to the human subjectone or more maintenance doses after the first maintenance dose is administered. In some embodiments, each of the one or more maintenance doses after the first maintenance dose independently contains the compound at an amount of from about 25 to about 100 mg. In some embodiments, each of the one or more maintenance doses after the first maintenance dose independently contains the compound at an amount of about 45 mg. In some embodiments, each of the one or more maintenance doses after the first maintenance dose independently contains the compound at an amount of about 70 mg.

[0016] In some embodiments, the compound has the following structure:(II) (the compound also referred to as “Compound-A” or “ASO-1” herein).

[0017] In some embodiments, the first loading dose contains the compound at an amount of about 20mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

[0018] In some embodiments, the first loading dose contains the compound at an amount of about 30mg. In some embodiments, the first loading dose contains the compound at an amount of about 70 mg.

[0019] In some embodiments, the first loading dose contains the compound at an amount of about 45mg. In some embodiments, the first loading dose contains the compound at an amount of about 50 mg. In some embodiments, the first loading dose contains the compound at an amount of from 25 mg to about 35 mg. In some embodiments, the first loading dose contains the compound at an amount of from 35 to 50 mg. In some embodiments, the first loading dose contains the compound at an amount of from 45 toWSGR Ref. No.: 47991-748.601 70 mg. In some embodiments, the first loading dose contains the compound at an amount of from 50 to 70 mg. In some embodiments, the first loading dose contains the compound at an amount of from 60 to 80 mg. In some embodiments, the first loading dose contains the compound at an amount of from 30 to 45 mg. In some embodiments, the first loading dose contains the compound at an amount of from 25 to 40 mg. In some embodiments, the first loading dose contains the compound at an amount of from 35 to 45 mg. In some embodiments, the first loading dose contains the compound at an amount of from 40 to 55 mg.

[0020] In some embodiments, the second loading dose contains the compound at an amount of about 20mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

[0021] In some embodiments, the second loading dose contains the compound at an amount of about 30mg. In some embodiments, the second loading dose contains the compound at an amount of about 70 mg. In some embodiments, the second loading dose contains the compound at an amount of about 45 mg. In some embodiments, the second loading dose contains the compound at an amount of about 50 mg. In some embodiments, the second loading dose contains the compound at an amount of from 25 mg to about 35 mg. In some embodiments, the second loading dose contains the compound at an amount of from 35 to 50 mg. In some embodiments, the second loading dose contains the compound at an amount of from 45 to 70 mg. In some embodiments, the second loading dose contains the compound at an amount of from 50 to 70 mg. In some embodiments, the second loading dose contains the compound at an amount of from 60 to 80 mg. In some embodiments, the second loading dose contains the compound at an amount of from 30 to 45 mg. In some embodiments, the second loading dose contains the compound at an amount of from 25 to 40 mg. In some embodiments, the second loading dose contains the compound at an amount of from 35 to 45 mg. In some embodiments, the second loading dose contains the compound at an amount of from 40 to 55 mg. In some embodiments, the second loading dose contains same amount of the compound as the first loading dose.

[0022] In some embodiments, the third loading dose contains the compound at an amount of about 20mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

[0023] In some embodiments, the third loading dose contains the compound at an amount of about 30mg. In some embodiments, the third loading dose contains the compound at an amount of about 70 mg. In some embodiments, the third loading dose contains the compound at an amount of about 45 mg. In some embodiments, the third loading dose contains the compound at an amount of about 50 mg. In some embodiments, the third loading dose contains the compound at an amount of from 25 mg to about 35 mg. In some embodiments, the third loading dose contains the compound at an amount of from 35 to 50 mg.WSGR Ref. No.: 47991-748.601 In some embodiments, the third loading dose contains the compound at an amount of from 45 to 70 mg. In some embodiments, the third loading dose contains the compound at an amount of from 50 to 70 mg. In some embodiments, the third loading dose contains the compound at an amount of from 60 to 80 mg. In some embodiments, the third loading dose contains the compound at an amount of from 30 to 45 mg. In some embodiments, the third loading dose contains the compound at an amount of from 25 to 40 mg. In some embodiments, the third loading dose contains the compound at an amount of from 35 to 45 mg. In some embodiments, the third loading dose contains the compound at an amount of from 40 to 55 mg. In some embodiments, the third loading dose contains same amount of the compound as the first loading dose.

[0024] In some embodiments, the first maintenance dose contains the compound at an amount of about20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

[0025] In some embodiments, each maintenance dose of the one or more maintenance dosesindependently contains the compound at an amount of about 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

[0026] In some embodiments, each maintenance dose of the one or more maintenance doses isadministered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.

[0027] In some embodiments, each maintenance dose of the one or more maintenance doses containssame amount of the compound. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of about 30 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of about 45 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of about 70 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 55 to 70 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 55 to 75 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 55 to 80 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 40 to 70 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 40 to 75 mg. In someWSGR Ref. No.: 47991-748.601 embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 40 to 80 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 65 to 90 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 65 to 95 mg. In some embodiments, the first maintenance dose and each maintenance dose of the one or more maintenance doses contains the compound at an amount of from 65 to 100 mg.

[0028] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains same amount of the compound as the first loading dose or the second loading dose.

[0029] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains same amount of the compound as the first loading dose, the second loading dose, or the third loading dose.

[0030] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contain a higher amount of the compound than the first loading dose or the second loading dose.

[0031] In some embodiments, the first maintenance dose or each maintenance dose of the one and moremaintenance doses contains the compound at an amount that is at least about 10%, 20%, or 30% higher than the amount in the first loading dose or the second loading dose.

[0032] In some embodiments, the first maintenance dose or each maintenance dose of the one and moremaintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg higher than the amount in the first loading dose or the second loading dose.

[0033] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contain a higher amount of the compound than the first loading dose, the second loading dose, or the third loading dose.

[0034] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains the compound at an amount that is at least about 10%, 20%, or 30% higher than the amount in the first loading dose, the second loading dose, or the third loading dose.

[0035] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg higher than the amount in the first loading dose, the second loading dose, or the third loading dose.

[0036] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contain a lower amount of the compound than the first loading dose or the second loading dose.

[0037] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains the compound at an amount that is at least about 10%, 20%, or 30% lower than the amount in the first loading dose or the second loading dose.WSGR Ref. No.: 47991-748.601

[0038] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg lower than the amount in the first loading dose or the second loading dose.

[0039] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contain a lower amount of the compound than the first loading dose, the second loading dose, or the third loading dose.

[0040] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains the compound at an amount that is at least about 10%, 20%, or 30% lower than the amount in the first loading dose, the second loading dose, or the third loading dose.

[0041] In some embodiments, the first maintenance dose and each maintenance dose of the one or moremaintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg lower than the amount in the first loading dose, the second loading dose, or the third loading dose.

[0042] In some embodiments, the second loading dose is administered from 4 weeks to 11 weeks, from4 weeks to 10 weeks, from 4 weeks to 9 weeks, from 4 weeks to 8 weeks, from 4 weeks to 7 weeks, from 4 weeks to 6 weeks, from 4 weeks to 5 weeks, from 5 weeks to 12 weeks, from 5 weeks to 11 weeks, from 5 weeks to 10 weeks, from 5 weeks to 9 weeks, from 5 weeks to 8 weeks, from 5 weeks to 7 weeks, from 5 weeks to 6 weeks, from 6 weeks to 12 weeks, from 6 weeks to 11 weeks, from 6 weeks to 10 weeks, from 6 weeks to 9 weeks, from 6 weeks to 8 weeks, from 6 weeks to 7 weeks, from 7 weeks to 12 weeks, from 7 weeks to 11 weeks, from 7 weeks to 10 weeks, from 7 weeks to 9 weeks, from 7 weeks to 8 weeks, from 8 weeks to 12 weeks, from 8 weeks to 11 weeks, from 8 weeks to 10 weeks, from 8 weeks to 9 weeks, from 9 weeks to 12 weeks, from 9 weeks to 11 weeks, from 9 weeks to 10 weeks, from 10 weeks to 12 weeks, from 10 weeks to 11 weeks, or from 11 weeks to 12 weeks after the first loading dose.

[0043] In some embodiments, the second loading dose is administered about 4 weeks, 5 weeks, 6 weeks,7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks after the first loading dose.

[0044] In some embodiments, the second loading dose is administered about 6 weeks after theadministration of the first loading dose. In some embodiments, the second loading dose is administered about 7 weeks after the administration of the first loading dose. In some embodiments, the second loading dose is administered about 8 weeks after the administration of the first loading dose. In some embodiments, the second loading dose is administered about 9 weeks after the administration of the first loading dose. In some embodiments, the second loading dose is administered about 10 weeks after the administration of the first loading dose.

[0045] In some embodiments, the third loading dose is administered from 4 weeks to 11 weeks, from 4weeks to 10 weeks, from 4 weeks to 9 weeks, from 4 weeks to 8 weeks, from 4 weeks to 7 weeks, from 4 weeks to 6 weeks, from 4 weeks to 5 weeks, from 5 weeks to 12 weeks, from 5 weeks to 11 weeks, from 5 weeks to 10 weeks, from 5 weeks to 9 weeks, from 5 weeks to 8 weeks, from 5 weeks to 7 weeks, from 5 weeks to 6 weeks, from 6 weeks to 12 weeks, from 6 weeks to 11 weeks, from 6 weeks to 10 weeks,WSGR Ref. No.: 47991-748.601 from 6 weeks to 9 weeks, from 6 weeks to 8 weeks, from 6 weeks to 7 weeks, from 7 weeks to 12 weeks, from 7 weeks to 11 weeks, from 7 weeks to 10 weeks, from 7 weeks to 9 weeks, from 7 weeks to 8 weeks, from 8 weeks to 12 weeks, from 8 weeks to 11 weeks, from 8 weeks to 10 weeks, from 8 weeks to 9 weeks, from 9 weeks to 12 weeks, from 9 weeks to 11 weeks, from 9 weeks to 10 weeks, from 10 weeks to 12 weeks, from 10 weeks to 11 weeks, or from 11 weeks to 12 weeks after the second loading dose.

[0046] In some embodiments, the third loading dose is administered about 4 weeks, 5 weeks, 6 weeks, 7weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks after the second loading dose.

[0047] In some embodiments, the third loading dose is administered about 4 weeks after theadministration of the second loading dose. In some embodiments, the third loading dose is administered about 5 weeks after the administration of the second loading dose. In some embodiments, the third loading dose is administered about 6 weeks after the administration of the second loading dose. In some embodiments, the third loading dose is administered about 7 weeks after the administration of the second loading dose. In some embodiments, the third loading dose is administered about 8 weeks after the administration of the second loading dose. In some embodiments, the third loading dose is administered about 9 weeks after the administration of the second loading dose. In some embodiments, the third loading dose is administered about 10 weeks after the administration of the second loading dose.

[0048] In some embodiments, the first loading dose, the second loading dose, and the third loading doseare administered about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks apart from each other. In some embodiments, the first loading dose, the second loading dose, and the third loading dose are administered about 6 weeks apart from each other. In some embodiments, the first loading dose, the second loading dose, and the third loading dose are administered about 7 weeks apart from each other. In some embodiments, the first loading dose, the second loading dose, and the third loading dose are administered about 8 weeks apart from each other. In some embodiments, the first loading dose, the second loading dose, and the third loading dose are administered about 9 weeks apart from each other. In some embodiments, the first loading dose, the second loading dose, and the third loading dose are administered about 10 weeks apart from each other.

[0049] In some embodiments, the first maintenance dose is administered from 8 weeks to 11 months,from 8 weeks to 10 months, from 8 weeks to 8 months, from 8 weeks to 6 months, from 8 weeks to 20 weeks, from 8 weeks to 16 weeks, from 8 weeks to 14 weeks, from 8 weeks to 12 weeks, from 8 weeks to 10 weeks, from 10 weeks to 12 weeks, from 12 weeks to 16 weeks, from 12 weeks to 12 months, from 12 weeks to 11 months, from 12 weeks to 12 months, from 12 weeks to 8 months, from 12 weeks to 6 months, from 12 weeks to 20 weeks, from 12 weeks to 16 weeks, from 12 weeks to 14 weeks, from 16 weeks to 12 months, from 16 weeks to 11 months, from 16 weeks to 10 months, from 16 weeks to 8 months, from 16 weeks to 6 months, from 16 weeks to 20 weeks, from 20 weeks to 12 months, from 20 weeks to 11 months, from 20 weeks to 10 months, from 20 weeks to 8 months, from 20 weeks to 6 months, from 6 months to 12 months, from 6 months to 11 months, from 6 months to 10 months, from 6 months to 9 months, from 6 months to 8 months, from 6 months to 7 months, from 7 months to 12WSGR Ref. No.: 47991-748.601 months, from 7 months to 11 months, from 7 months to 10 months, from 7 months to 9 months, from 7 months to 8 months, from 8 months to 12 months, from 8 months to 11 months, from 8 months to 10 months, from 8 months to 9 months, from 9 months to 12 months, from 9 months to 11 months, from 9 months to 10 months, from 10 months to 12 months, from 10 months to 11 months, or from 11 months to 12 months after the second loading dose.

[0050] In some embodiments, the first maintenance dose is administered about 8 weeks, 9 weeks, 10weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 22 weeks, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months after the second loading dose.

[0051] In some embodiments, the first maintenance dose is administered about 8 weeks after the secondloading dose. In some embodiments, the first maintenance dose is administered about 12 weeks after the second loading dose. In some embodiments, the first maintenance dose is administered about 16 weeks after the second loading dose. In some embodiments, the first maintenance dose is administered about 20 weeks after the second loading dose. In some embodiments, the first maintenance dose is administered about 4 months after the second loading dose. In some embodiments, the first maintenance dose is administered about 6 months after the second loading dose. In some embodiments, the first maintenance dose is administered about 9 months after the second loading dose. In some embodiments, the first maintenance dose is administered about 12 months after the second loading dose.

[0052] In some embodiments, the first maintenance dose is administered from 8 weeks to 11 months,from 8 weeks to 10 months, from 8 weeks to 8 months, from 8 weeks to 6 months, from 8 weeks to 20 weeks, from 8 weeks to 16 weeks, from 8 weeks to 14 weeks, from 8 weeks to 12 weeks, from 8 weeks to 10 weeks, from 10 weeks to 12 weeks, from 12 weeks to 16 weeks, from 12 weeks to 12 months, from 12 weeks to 11 months, from 12 weeks to 12 months, from 12 weeks to 8 months, from 12 weeks to 6 months, from 12 weeks to 20 weeks, from 12 weeks to 16 weeks, from 12 weeks to 14 weeks, from 16 weeks to 12 months, from 16 weeks to 11 months, from 16 weeks to 10 months, from 16 weeks to 8 months, from 16 weeks to 6 months, from 16 weeks to 20 weeks, from 20 weeks to 12 months, from 20 weeks to 11 months, from 20 weeks to 10 months, from 20 weeks to 8 months, from 20 weeks to 6 months, from 6 months to 12 months, from 6 months to 11 months, from 6 months to 10 months, from 6 months to 9 months, from 6 months to 8 months, from 6 months to 7 months, from 7 months to 12 months, from 7 months to 11 months, from 7 months to 10 months, from 7 months to 9 months, from 7 months to 8 months, from 8 months to 12 months, from 8 months to 11 months, from 8 months to 10 months, from 8 months to 9 months, from 9 months to 12 months, from 9 months to 11 months, from 9 months to 10 months, from 10 months to 12 months, from 10 months to 11 months, or from 11 months to 12 months after the third loading dose.

[0053] In some embodiments, the first maintenance dose is administered about 8 weeks, 9 weeks, 10weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 22 weeks, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months after the third loading dose.WSGR Ref. No.: 47991-748.601

[0054] In some embodiments, the first maintenance dose is administered about 8 weeks after the thirdloading dose. In some embodiments, the first maintenance dose is administered about 12 weeks after the third loading dose. In some embodiments, the first maintenance dose is administered about 16 weeks after the third loading dose. In some embodiments, the first maintenance dose is administered about 20 weeks after the third loading dose. In some embodiments, the first maintenance dose is administered about 4 months after the third loading dose. In some embodiments, the first maintenance dose is administered about 6 months after the third loading dose. In some embodiments, the first maintenance dose is administered about 9 months after the third loading dose. In some embodiments, the first maintenance dose is administered about 12 months after the third loading dose. In some embodiments, the one or more maintenance doses consist of one maintenance dose.

[0055] In some embodiments, the one or more maintenance doses comprise at least two maintenancedoses, and wherein each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered independently from 8 weeks to 11 months, from 8 weeks to 10 months, from 8 weeks to 8 months, from 8 weeks to 6 months, from 8 weeks to 20 weeks, from 8 weeks to 16 weeks, from 8 weeks to 14 weeks, from 8 weeks to 12 weeks, from 8 weeks to 10 weeks, from 10 weeks to 12 weeks, from 12 weeks to 16 weeks, from 12 weeks to 12 months, from 12 weeks to 11 months, from 12 weeks to 12 months, from 12 weeks to 8 months, from 12 weeks to 6 months, from 12 weeks to 20 weeks, from 12 weeks to 16 weeks, from 12 weeks to 14 weeks, from 16 weeks to 12 months, from 16 weeks to 11 months, from 16 weeks to 10 months, from 16 weeks to 8 months, from 16 weeks to 6 months, from 16 weeks to 20 weeks, from 20 weeks to 12 months, from 20 weeks to 11 months, from 20 weeks to 10 months, from 20 weeks to 8 months, from 20 weeks to 6 months, from 6 months to 12 months, from 6 months to 11 months, from 6 months to 10 months, from 6 months to 9 months, from 6 months to 8 months, from 6 months to 7 months, from 7 months to 12 months, from 7 months to 11 months, from 7 months to 10 months, from 7 months to 9 months, from 7 months to 8 months, from 8 months to 12 months, from 8 months to 11 months, from 8 months to 10 months, from 8 months to 9 months, from 9 months to 12 months, from 9 months to 11 months, from 9 months to 10 months, from 10 months to 12 months, from 10 months to 11 months, or from 11 months to 12 months after the dose immediately preceding the respective maintenance dose.

[0056] In some embodiments, each maintenance dose of the one or more maintenance doses other thanthe first maintenance dose is administered independently about 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 22 weeks, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months after the dose immediately preceding the respective maintenance dose.

[0057] In some embodiments, each maintenance dose of the one or more maintenance doses other thanthe first maintenance dose is administered about 8 weeks after the dose immediately preceding the respective maintenance dose. In some embodiments, each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered about 12 weeks after the dose immediately preceding the respective maintenance dose. In some embodiments, each maintenance doseWSGR Ref. No.: 47991-748.601 of the one or more maintenance doses other than the first maintenance dose is administered about 16 weeks after the dose immediately preceding the respective maintenance dose. In some embodiments, each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered about 20 weeks after the dose immediately preceding the respective maintenance dose. In some embodiments, each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered about 4 months after the dose immediately preceding the respective maintenance dose. In some embodiments, each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered about 6 months after the dose immediately preceding the respective maintenance dose. In some embodiments, each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered about 9 months after the dose immediately preceding the respective maintenance dose. In some embodiments, each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered about 12 months after the dose immediately preceding the respective maintenance dose.

[0058] In some embodiments, the one or more maintenance doses consist of two maintenance doses. Insome embodiments, the one or more maintenance doses consist of three maintenance doses. In some embodiments, the one or more maintenance doses consist of four maintenance doses. In some embodiments, the one or more maintenance doses consist of five, six, seven, eight, or more maintenance doses. In some embodiments, the one or more maintenance doses comprise more than three maintenance doses.

[0059] In some embodiments, the one or more maintenance doses are administered over a lifetime of thehuman subject. In some embodiments, the method or the dosing regimen comprises administering the one or more maintenance doses to the human subject until an indication that a most recent maintenance dose is not tolerated by the human subject. In some embodiments, the one or more maintenance doses are administered to the human subject over a period of at least one year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 15 years, 20 years, 25 years, 30 years, 35, years, 40 years, 45 years, 50 years, 55 years, or 60 years.

[0060] In some embodiments, each dose of the first loading dose and the second loading dose containsthe compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg.

[0061] In some embodiments, each dose of the first loading dose and the second loading dose containsthe compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 70 mg.

[0062] In some embodiments, each dose of the first loading dose, the second loading dose and the thirdloading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 70 mg.

[0063] In some embodiments, each dose of the first loading dose, the second loading dose and the thirdloading dose contains the compound at an amount of about 70 mg, wherein the first maintenance doseWSGR Ref. No.: 47991-748.601 and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg.

[0064] In some embodiments, the second loading dose is administered about 8 weeks after the firstloading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose of the after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

[0065] In some embodiments, the second loading dose is administered about 8 weeks after the firstloading dose, the third loading dose is administered about 4 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

[0066] In some embodiments, the one or more maintenance doses are administered at a same dosefrequency or a substantially same dose frequency.

[0067] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof,WSGR Ref. No.: 47991-748.601 wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.

[0068] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0069] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.

[0070] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:WSGR Ref. No.: 47991-748.601(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.

[0071] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the one or more maintenance doses is about 30 mg.

[0072] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the one or more maintenance doses is about 45 mg.

[0073] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the one or more maintenance doses is about 50 mg.

[0074] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the one or more maintenance doses is about 60 mg.

[0075] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the one or more maintenance doses is about 70 mg.WSGR Ref. No.: 47991-748.601

[0076] In some embodiments, the amount of the compound in each dose of the first loading dose and thesecond loading dose is about 30 mg, and the amount of the compound in each of the one or more maintenance doses is about 25 mg.

[0077] In some embodiments, the amount of the compound in each dose of the first loading dose and thesecond loading dose is about 45 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg.

[0078] In some embodiments, the amount of the compound in each dose of the first loading dose and thesecond loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg.

[0079] In some embodiments, the amount of the compound in each dose of the first loading dose and thesecond loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg.

[0080] In some embodiments, the amount of the compound in each dose of the first loading dose and thesecond loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg.

[0081] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof,WSGR Ref. No.: 47991-748.601 wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.

[0082] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose,WSGR Ref. No.: 47991-748.601 wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 8 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

[0083] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg,WSGR Ref. No.: 47991-748.601 wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 10 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.

[0084] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 12 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 6 months after the third loading dose, and each maintenance after the first maintenance dose is administeredWSGR Ref. No.: 47991-748.601 independently about 6 months after a dose immediately preceding the respective maintenance dose.

[0085] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 3 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0086] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 4 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0087] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 5 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0088] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 to about 80 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 6 months after the third loading dose, and each maintenance after the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0089] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 30 mg.

[0090] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 45 mg.

[0091] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 50 mg.

[0092] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 60 mg.

[0093] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 70 mg.

[0094] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the third loading dose is about 30 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 25 mg.

[0095] In some embodiments, the amount of the compound in each dose of the amount of the compoundin each of the first loading dose, the second loading dose, and the third loading dose is about 45 mg, and the first maintenance dose and the one or more maintenance doses is about 40 mg.

[0096] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the third loading dose is about 50 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 45 mg.

[0097] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 45 mg.

[0098] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 45 mg.WSGR Ref. No.: 47991-748.601

[0099] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0100] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0101] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0102] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 6 months after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0103] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0104] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 8 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0105] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 10 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0106] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 12 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0107] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 3 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0108] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 4 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0109] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 5 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0110] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0111] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0112] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0113] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0114] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 6 months after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0115] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0116] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 8 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0117] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 10 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0118] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 12 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0119] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 3 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0120] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 4 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0121] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 5 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0122] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0123] In some embodiments, the compound has the following structure:(II).

[0124] In some embodiments, the pharmaceutical composition further comprises a pharmaceuticallyacceptable excipient, carrier, or diluent.

[0125] In some embodiments, the pharmaceutical composition is a liquid composition.

[0126] In some embodiments, the pharmaceutical composition comprises from 0.1 mL to 50 mL of adiluent, and wherein the compound is solubilized or diluted in the diluent.

[0127] In some embodiments, the pharmaceutical composition comprises about 0.1 mL, 0.5 mL, 1 mL, 2mL, 2.5 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, 15 mL, 16 mL, 17 mL, 18 mL, 19 mL, 20 mL, 25 mL, 30 mL, 35 mL, 40 mL, 45 mL, or 50 mL of the diluent.

[0128] In some embodiments, the pharmaceutical composition comprises 1 mL to 20 mL of the diluent,2 mL to 10 mL of the diluent, or 1 mL to 5 mL of the diluent.

[0129] In some embodiments, the pharmaceutical composition comprises at least 4 mL, 5 mL, 6 mL, 7mL, 8 mL, 9 mL, or 10 mL of the diluent.

[0130] In some embodiments, the pharmaceutical composition comprises about 4 mL, 5 mL, 6 mL, 7mL, 8 mL, 9 mL, or 10 mL of the diluent.

[0131] In some embodiments, the pharmaceutical composition comprises about 4 mL of the diluent.

[0132] In some embodiments, the pharmaceutical composition comprises about 7 mL of the diluent.

[0133] In some embodiments, the pharmaceutical composition comprises about 9 mL of the diluent.

[0134] In some embodiments, the pharmaceutical composition comprises about 10 mL of the diluent.WSGR Ref. No.: 47991-748.601

[0135] In some embodiments, the compound is dissolved or diluted in the diluent and the first loadingdose has volume of 10 mL or higher.

[0136] In some embodiments, the compound is dissolved or diluted in the diluent and the first loadingdose has volume of 5 mL or higher.

[0137] In some embodiments, the compound is dissolved or diluted in the diluent and the first loadingdose has volume of about 10 mL.

[0138] In some embodiments, the compound is dissolved or diluted in the diluent and the first loadingdose has volume of about 15 mL.

[0139] In some embodiments, the compound is dissolved or diluted in the diluent and the first loadingdose has volume of about 20 mL.

[0140] In some embodiments, the compound is dissolved or diluted in the diluent and the first loadingdose has volume of about 25 mL.

[0141] In some embodiments, the compound is dissolved or diluted in the diluent and the first loadingdose has volume of about 30 mL.

[0142] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of 5 mL or higher.

[0143] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of 10 mL or higher.

[0144] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of about 5 mL.

[0145] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of about 10 mL.

[0146] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of about 15 mL.

[0147] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of about 20 mL.

[0148] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of about 25 mL.

[0149] In some embodiments, the compound is dissolved or diluted in the diluent and each maintenancedose of the one or more maintenance doses has a volume of about 30 mL.

[0150] In some embodiments, the diluent comprises a cerebral spinal fluid (CSF) sample from thesubject or an artificial cerebral spinal fluid (aCSF) solution.

[0151] In some embodiments, the diluent is the aCSF solution that lacks sodium phosphate.

[0152] In some embodiments, each dose of the pharmaceutical composition comprises 10 mL of thediluent.

[0153] In some embodiments, the diluent is an isotonic solution.

[0154] In some embodiments, the diluent is a solution with at least pH 5.8.

[0155] In some embodiments, the diluent is a solution with pH 6.6 – 7.6.WSGR Ref. No.: 47991-748.601

[0156] In some embodiments, the diluent is a buffer comprising 25-250 mM NaCl.

[0157] In some embodiments, the diluent is a buffer comprising 0.1-20 mM KCl.

[0158] In some embodiments, the diluent is a buffer comprising 0.1-50 mM Na2HPO4.

[0159] In some embodiments, the diluent is a buffer comprising 0.1-50 mM NaH2PO4.

[0160] In some embodiments, the diluent is a buffer comprising 0.1-50 mM CaCl2.

[0161] In some embodiments, the diluent is a buffer comprising 0.1-50 mM MgCl2.

[0162] In some embodiments, the diluent is a buffer comprising 150 mM NaCl, 3.0 mM KCl, 0.7 mMNa2HPO4, 0.3 mM NaH2PO4, 0.79 mM MgCl2, and 1.4 mM CaCl2.

[0163] In some embodiments, the diluent is a buffer further comprising 1-100 mM NaHCO3, 1-100 mMKHCO3, or a combination thereof.

[0164] In some embodiments, the diluent further comprises carbohydrates.

[0165] In some embodiments, the carbohydrates comprise D-glucose.

[0166] In some embodiments, the diluent comprises 1-100 mM D-glucose.

[0167] In some embodiments, the pharmaceutical composition comprises 0.1-50 mM CaCl2 orCaCl2·2H2O.

[0168] In some embodiments, the pharmaceutical composition comprises 1-2 mM CaCl2 or CaCl2·2H2O.

[0169] In some embodiments, the pharmaceutical composition comprises about 1.4 mM CaCl2 orCaCl2·2H2O.

[0170] In some embodiments, the pharmaceutical composition further comprises 0.1-50 mM MgCl2 orMgCl2·6H2O.

[0171] In some embodiments, the pharmaceutical composition comprises 0.5-1.5 mM MgCl2 orMgCl2·6H2O.

[0172] In some embodiments, the pharmaceutical composition comprises about 0.79 mM MgCl2 orMgCl2·6H2O.

[0173] In some embodiments, the pharmaceutical composition comprises 5-250 mM NaCl, 0.1-20 mMKCl, 0.1-50 mM CaCl2or CaCl2·2H2O, and 0.1-50 mM MgCl2or MgCl2·6H2O.

[0174] In some embodiments, the pharmaceutical composition comprises the compound at aconcentration of about 0.1 mg / mL to about 500 mg / mL, (a) calcium chloride (CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) at a concentration of about 0.1 mM to about 50 mM; (b) magnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) at a concentration of about 0.1 mM to about 50 mM; (c) potassium chloride (KCl) at a concentration of about 0.1 mM to about 20 mM; (d) sodium chloride (NaCl) at a concentration of about 25 mM to about 250 mM; and (e) water.

[0175] In some embodiments, the concentration of calcium chloride (CaCl2) or calcium chloridedihydrate (CaCl2·2H2O) is 0.2 mM to 25 mM, 0.5 mM to 10 mM, 0.75 mM to 5 mM, or 1 mM to 2 mM.

[0176] In some embodiments, the concentration of calcium chloride (CaCl2) or calcium chloridedihydrate (CaCl2·2H2O) is from about 1 mM to about 2 mM.

[0177] In some embodiments, the concentration of calcium chloride (CaCl2) or calcium chloridedihydrate (CaCl2·2H2O) is about 1.4 mM.WSGR Ref. No.: 47991-748.601

[0178] In some embodiments, the concentration of magnesium chloride (MgCl2) or magnesium chloridehexahydrate (MgCl2·6H2O) is 0.2 mM to 25 mM, 0.3 mM to 15 mM, 0.4 mM to 5 mM, 0.5 mM to 1.5 mM, or 0.6 mM to 1 mM.

[0179] In some embodiments, the concentration of magnesium chloride (MgCl2) or magnesium chloridehexahydrate (MgCl2·6H2O) is from about 0.6 mM to about 1 mM.

[0180] In some embodiments, the concentration of magnesium chloride (MgCl2) or magnesium chloridehexahydrate (MgCl2·6H2O) is about 0.79 mM.

[0181] In some embodiments, the concentration of potassium chloride is 0.5 mM to 10 mM, 1 mM to7.5 mM, or 2 mM to 5 mM.

[0182] In some embodiments, the concentration of potassium chloride is from about 2 mM to about 5mM.

[0183] In some embodiments, the concentration of potassium chloride is about 3 mM.

[0184] In some embodiments, the concentration of sodium chloride is 25 mM to 250 mM, 100 mM to160 mM, 110 mM to 140 mM, or 130 mM to 160 mM.

[0185] In some embodiments, the concentration of sodium chloride is from about 125 mM to 145 mM.

[0186] In some embodiments, the concentration of sodium chloride is about 130 mM.

[0187] In some embodiments, the concentration of sodium chloride is from about 140 mM to 160 mM.

[0188] In some embodiments, the concentration of sodium chloride is about 150 mM.

[0189] In some embodiments, the pharmaceutical composition comprises the compound at aconcentration of about 0.1 mg / mL to about 500 mg / mL, (a) calcium ion (Ca2+) at a concentration of about 0.1 mM to about 50 mM; (b) magnesium ion (Mg2+) at a concentration of about 0.1 mM to about 50 mM; (c) potassium ion (K+) at a concentration of about 0.1 mM to about 20 mM; (d) sodium ion (Na+) at a concentration of about 25 mM to about 250 mM; (e) chloride ion (Cl-) at a concentration of about 25 mM to about 250 mM; and (f) water.

[0190] In some embodiments, the pharmaceutical composition comprises the compound at aconcentration of about 0.1 mg / mL to about 500 mg / mL, (a) calcium ion (Ca2+) at a concentration of about 1.4 mM; (b) magnesium ion (Mg2+) at a concentration of about 0.79 mM; (c) potassium ion (K+) at a concentration of about 3 mM; (d) sodium ion (Na+) at a concentration of about 160 mM; (e) chloride ion (Cl-) at a concentration of about 160 mM; and (f) water.

[0191] In some embodiments, the pharmaceutical composition lacks Na2HPO4 and / or NaH2PO4.

[0192] In some embodiments, the pharmaceutical composition lacks phosphate ion.

[0193] In some embodiments, each dose of the pharmaceutical composition comprises 10 mL of thediluent.WSGR Ref. No.: 47991-748.601

[0194] In some embodiments, the diluent further comprises an antioxidant.

[0195] In some embodiments, the antioxidant is t-butylhydroxyquinoline (TBHQ), butylatedhydroxytoluene (BHT), butylated hydroxyanisole (BHA), vitamin E, or any combination thereof.

[0196] In some embodiments, the pharmaceutical composition is administered into the intrathecal spaceof the human subject.

[0197] In some embodiments, the pharmaceutical composition is administered into the cerebrospinalfluid of the human subject.

[0198] In some embodiments, the pharmaceutical composition is administered into the brain of thehuman subject.

[0199] In some embodiments, the pharmaceutical composition is administered into the cerebrospinalfluid in the brain of the human subject.

[0200] In some embodiments, the pharmaceutical composition is administered as a bolus injection.

[0201] In some embodiments, the method or the dosing regimen comprises administering thepharmaceutical composition as a bolus injection over 1 to 60 minutes, 1 to 50 minutes, 1 to 40 minutes, 1 to 30 minutes, 1 to 20 minutes, 1 to 10 minutes, 1 to 5 minutes, or 1 to 3 minutes.

[0202] In some embodiments, the pharmaceutical composition is administered by infusion with adelivery pump.

[0203] In some embodiments, the pharmaceutical composition is administered byintracerebroventricular injection.

[0204] In some embodiments, the pharmaceutical composition is administered by intrathecal injection.

[0205] In some embodiments, each dose of the pharmaceutical composition comprises a diluent of avolume of 10 mL, and the diluent is an aCSF solution that lacks sodium phosphate.

[0206] In some embodiments, the pharmaceutical composition is administered by lumbar injection.

[0207] In some embodiments, the pharmaceutical composition does not comprise a preservative.

[0208] In some embodiments, the concentration of the compound in the pharmaceutical composition isabout 0.1 mg / mL to about 250 mg / mL.

[0209] In some embodiments, the concentration of the compound in the pharmaceutical composition isfrom 6.7 mg / mL to 188 mg / mL, from 6.8 mg / mL to 187 mg / mL, from 3 mg / mL to 100 mg / mL, or from 3 mg / mL to 33 mg / mL.

[0210] In some embodiments, the concentration of the compound in the pharmaceutical composition isabout 0.1 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 2.5 mg / mL, 3 mg / mL, 4 mg / mL, 4.5 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 17 mg / mL, 18 mg / mL, 19 mg / mL, 20 mg / mL, 22 mg / mL, 25 mg / mL, 28 mg / mL, or 33 mg / mL.

[0211] In some embodiments, the concentration of the compound in the pharmaceutical composition is11 mg / mL, 22 mg / mL, 33 mg / mL, 44 mg / mL, 55 mg / mL, 66 mg / mL, 77 mg / mL, 88 mg / mL, 99 mg / mL, or 100 mg / mL.WSGR Ref. No.: 47991-748.601

[0212] In some embodiments, the concentration of the compound in the pharmaceutical composition isabout 3 mg / mL, 4 mg / mL, 4.5 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 17 mg / mL, 18 mg / mL, 19 mg / mL, 20 mg / mL, 22.5 mg / mL, 25 mg / mL, 27.5 mg / mL, 30 mg / mL, 32.5 mg / mL, 35 mg / mL, 37.5 mg / mL, 40 mg / mL, 42.5 mg / mL, 45 mg / mL, 47.5 mg / mL, 50 mg / mL, 52.5 mg / mL, 55 mg / mL, 57.5 mg / mL, 60 mg / mL, 62.5 mg / mL, 65 mg / mL, 67.5 mg / mL, 70 mg / mL, 72.5 mg / mL, 75 mg / mL, 77.5 mg / mL, 80 mg / mL, 82.5 mg / mL, 85 mg / mL, 87.5 mg / mL, 90 mg / mL, 92.5 mg / mL, 95 mg / mL, 97.5 mg / mL, 100 mg / mL, 102.5 mg / mL, 105 mg / mL, 107.5 mg / mL, 110 mg / mL, 112.5 mg / mL, 115 mg / mL, 117.5 mg / mL, 120 mg / mL, 122.5 mg / mL, 125 mg / mL, 127.5 mg / mL, 130 mg / mL, 132.5 mg / mL, 135 mg / mL, 137.5 mg / mL, 140 mg / mL, 142.5 mg / mL, 145 mg / mL, 147.5 mg / mL, 150 mg / mL, 152.5 mg / mL, 155 mg / mL, 157.5 mg / mL, 160 mg / mL, 162.5 mg / mL, 165 mg / mL, 167.5 mg / mL, 170 mg / mL, 172.5 mg / mL, 175 mg / mL, 177.5 mg / mL, 180 mg / mL, 182.5 mg / mL, 185 mg / mL, 187.5 mg / mL, 190 mg / mL, 192.5 mg / mL, 195 mg / mL, 197.5 mg / mL, 200 mg / mL, 202.5 mg / mL, 205 mg / mL, 207.5 mg / mL, 210 mg / mL, 212.5 mg / mL, 215 mg / mL, 217.5 mg / mL, 220 mg / mL, 222.5 mg / mL, 225 mg / mL, 227.5 mg / mL, 230 mg / mL, 232.5 mg / mL, 235 mg / mL, 237.5 mg / mL, 240 mg / mL, 242.5 mg / mL, 245 mg / mL, 247.5 mg / mL, or 250 mg / mL.

[0213] In some embodiments, the human subject is at most 18 years old at first loading dose.

[0214] In some embodiments, the human subject is at least 2 years old.

[0215] In some embodiments, the human subject is at least 6 months old.

[0216] In some embodiments, the human subject is from 6 months to 1 year old, or from 1 to 18, from 2to 18, from 3 to 18, from 4 to 18, from 5 to 18, from 6 to 18, from 7 to 18, from 8 to 18, from 9 to 18, from 10 to 18, from 11 to 18, from 12 to 18, from 13 to 18, from 14 to 18, from 15 to 18, from 16 to 18, or from 17 to 18 years old.

[0217] In some embodiments, the human subject is a human from 6 months to 1 year old, or from 1 to17, from 1 to 16, from 1 to 15, from 1 to 14, from 1 to 13, from 1 to 12, from 1 to 11, from 1 to 10, from 1 to 9, from 1 to 8, from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 1 to 3, or from 1 to 2 years old.

[0218] In some embodiments, the human subject is from 2 to 12 years old.

[0219] In some embodiments, the human subject is from 13 to 18 years old.

[0220] In some embodiments, the human subject is at least 13 years old.

[0221] In some embodiments, the race of the human subject is white.

[0222] In some embodiments, the race of the human subject is Asian.

[0223] In some embodiments, the race of the human subject is black or African American

[0224] In some embodiments, the human subject receives administration of at least one concomitantanti-seizure medication.

[0225] In some embodiments, the human subject receives administration of at least 3 or 4 concomitantanti-seizure medications.

[0226] In some embodiments, the human subject receives administration of fenfluramine.

[0227] In some embodiments, the disease or condition is treated.WSGR Ref. No.: 47991-748.601

[0228] In some embodiments, the disease or condition is Dravet Syndrome.

[0229] In some embodiments, the subject is characterized by having:(i) seizure onset prior to 12 months of age with recurrent focal motor or hemiconvulsive or generalized tonic-clonic seizures, which are often prolonged and triggered by hyperthermia; (ii) no past history of causal magnetic resonance imaging lesion; (iii) no other known etiology of any diseases or conditions except Dravet Syndrome; (iv) normal development at seizure onset; (v) a pathogenic variant, or variant of uncertain significance in an SCN1A gene; (vi) at least 2 prior treatments for epilepsy that either had lack of adequate seizure control; (vii) 4 or more convulsive seizures during the 28 days prior to administering, wherein the convulsive seizures is any one selected from Hemiclonic, Focal with Motor Signs, Focal to Bilateral Tonic Clonic Convulsion, Generalized Tonic Clonic Convulsion, Tonic, Tonic or Atonic (Drop Attacks), and Clonic; (viii) a current intervention for epilepsy or medication with at least one antiepileptic drug at a dose which has been stable for at least 4 weeks, wherein the intervention for epilepsy is a ketogenic diet, a vagal nerve stimulator, or a cannabinoid or marijuana-derived product; or (ix) any combination of (i) – (viii).

[0230] In some embodiments, the subject is additionally characterized by not having one or more of thefollowing: (a) one of the following mutations in the SCN1A gene: Thr226Met, Leu263Val, Val422Leu,Thr1174Ser, Trp1204Arg, Pro1345Ser, Gln1489Lys, Phe1499Leu, Arg1575Cys, Val1611Phe, Leu1624Pro, Arg1648Cys, Leu1649Gln, Leu1670Trp, Gly1674Arg, and Asp1866Tyr; (b) a known pathogenic mutation in another gene that causes epilepsy, wherein the pathogenicmutation is homozygous in cases of known recessive disease; (c) currently treated with a sodium channel blocker as maintenance treatment and ananticoagulant, wherein the sodium channel blocker is phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide, and wherein the anticoagulant is not an aspirin; (d) clinically, significantly unstable medical conditions other than epilepsy;(e) clinically, relevant symptoms or a clinically significant illness in the 4 weeks prior toadministering, other than epilepsy; (f) a history of brain or spinal cord disease other than epilepsy, Dravet Syndrome or a history ofbacterial meningitis or brain malformation; (g) a spinal deformity or other condition that alters the free flow of cerebrospinal fluid (CSF) orhaving an implanted CSF drainage shunt; (h) clinically significant abnormal laboratory values prior to administering;(i) aspartate aminotransferase or alanine aminotransferase >2.5-fold upper limit of normal,serum creatinine greater than an upper limit of normal or platelet count less than a lower limit of normal;WSGR Ref. No.: 47991-748.601 (j) clinically relevant abnormalities in the 12-lead electrocardiogram (ECG) measured at prior toadministering; (k) a psychiatric or behavioral disorder;(l) currently or in the past 4 weeks, medication of an anticoagulant, wherein the anticoagulant isnot aspirin; or (m) any combination of (a) – (l).

[0231] In some embodiments, the human subject comprises a deletion, a truncation, a missense, or anonsense mutation in SCN1A gene.

[0232] In some embodiments, at least one symptom of Dravet Syndrome in the human subject isreduced or ameliorated.

[0233] In some embodiments, the symptom of Dravet Syndrome is a seizure.

[0234] In some embodiments, the method or the dosing regimen reduces or ameliorates seizurefrequency, seizure intensity, and / or seizure duration.

[0235] In some embodiments, the reduction or amelioration of seizure frequency, seizure intensity,and / or seizure duration is sustained for at least 6 months, 9 months, 12 months, 15 months, 18 months, 24 months, 2.5 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 12 years, 14 years, 16 years, 18 years, or longer.

[0236] In some embodiments, the method or the dosing regimen results in an improvement in a non-seizure-related aspect.

[0237] In some embodiments, the improvement in the non-seizure-related aspect is sustained for at least6 months, 8 months, 12 months, 15 months, 18 months, 24 months, 2.5 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 12 years, 14 years, 16 years, 18 years, or longer.

[0238] In some embodiments, the non-seizure-related aspect comprises a cognitive or behavioral domainselected from the group consisting of communication, daily living skills, socialization and motor skills, and / or wherein the non-seizure-related aspect comprises a cognitive or behavioral subdomain selected from the group consisting of receptive communication, expressive communication, writing skills, personal skills, domestic skills, community skills, interpersonal relationships, play and leisure, coping skills, gross motor skills, and fine motor skills.

[0239] In some embodiments, the cognitive or behavioral aspect is determined according to astandardized assessment.

[0240] In some embodiments, the standardized assessment comprises a Vineland Adaptive BehaviorScale, Third Edition (VABS-III); a Clinical Global Impression of Change (CGI-C); or a Caregiver Global Impression of Change (CaGI-C); or any combination thereof.

[0241] In some embodiments, (i) the standardized assessment comprises VABS-III and the improvementis a positive change in a Gross Scale Value (GSV); (ii) the standardized assessment comprises CGI-C and the improvement is a CGI-C score of 3, 2, or 1; or (iii) the standardized assessment comprises CaGI-C and the improvement is a CaGI-C score of 3, 2, or 1.WSGR Ref. No.: 47991-748.601

[0242] In some embodiments, the standardized assessment comprises VABS-III and the positive changein GSV is at least 0.7000, 0.8000, 0.9000, 1.000, 1.250, 1.500, 1.750, 2.000, 2.250, 2.500, 2.750, 3.000, 3.250, 3.500, 3.750, 4.000, 4.250, 4.500, 4.750, 5.000, 5.250, 5.500, 5.750, 6.000, 7.000, 8.000, or 9.000.

[0243] In some embodiments, the standardized assessment comprises CGI-C and the improvement is aCGI-C score of 2 or 1.

[0244] In some embodiments, the standardized assessment comprises CaGI-C and the improvement is aCaGI-C score of 2 or 1.

[0245] In some embodiments, the administration (a) reduces or ameliorates seizure frequency, seizureintensity, and / or seizure duration; and (b) results in an improvement in a non-seizure-related aspect.

[0246] In some embodiments, the method or the dosing regimen results in no treatment-emergentserious adverse event (TESAE) in the human subject related to the administration of the compound of formula (I) or a salt thereof.

[0247] In some embodiments, the method or the dosing regimen further comprises assessing tolerabilityor effectiveness of the pharmaceutical composition.

[0248] In some embodiments, the method or the dosing regimen further comprises administrating atleast one additional therapeutic agent or therapy.

[0249] In some embodiments, the at least one additional therapeutic agent or therapy is administered atthe same time as the first loading dose, the second loading dose and / or the third loading dose.

[0250] In some embodiments, the at least one additional therapeutic agent or therapy is administered atthe same time as the first maintenance dose and / or the one or more further maintenance doses.

[0251] In some embodiments, the at least one additional therapeutic agent or therapy is administeredprior to administration of the first loading dose.

[0252] In some embodiments, the at least one additional therapeutic agent or therapy is administeredafter administration of the first loading dose.

[0253] In some embodiments, the at least one additional therapeutic agent or therapy comprisesfenfluramine.

[0254] In some embodiments, a predicted brain concentration of the compound in the subject afteradministration of the pharmaceutical composition is at least 1, 2, 4, 6, 8, or 10 µg / mL.

[0255] In some embodiments, the compound in the mean brain without thalamus of the subject ismaintained at a concentration between 5 µg / g and 40 µg / g following intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof and intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof.

[0256] In some embodiments, the compound in the mean brain without thalamus of the subject ismaintained at a concentration between 5 µg / g and 40 µg / g following intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the third loading dose comprising 70 mg of the compound ofWSGR Ref. No.: 47991-748.601 formula (I) or a salt thereof, and intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.

[0257] In some embodiments, the compound in the mean brain without thalamus of the subject ismaintained at a concentration within the range of about 20% to 140% of about 26 µg / g after intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof and intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof.

[0258] In some embodiments, the compound in the mean brain without thalamus of the subject ismaintained at a concentration within the range of about 20% to 140% of about 26 µg / g after intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the third loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, and intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.

[0259] In some embodiments, after intrathecal administration of the first loading dose comprising 70 mgof the compound of formula (I) or a salt thereof, the compound of formula (I) or a salt thereof formulated in the pharmaceutical composition provides a maximum brain without thalamus concentration within the range of about 80% to 125% of about 26 µg / g following intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof.

[0260] In some embodiments, after intrathecal administration of the first loading dose comprising 70 mgof the compound of formula (I) or a salt thereof and intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, the compound of formula (I) or a salt thereof formulated in the pharmaceutical composition provides a maximum brain without thalamus concentration within the range of about 80% to 125% of about 26 µg / g following intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.

[0261] In some embodiments, after intrathecal administration of the first loading dose comprising 70 mgof the compound of formula (I) or a salt thereof, intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, and intrathecal administration of the third loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, the compound of formula (I) or a salt thereof formulated in the pharmaceutical composition provides a maximum brain without thalamus concentration within the range of about 80% to 125% of about 26 µg / g following intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.WSGR Ref. No.: 47991-748.601

[0262] Provided herein, in some aspects, is a method of improving a non-seizure-related aspect in ahuman subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, thereby improving a non-seizure-related aspect in the human subject, wherein the non-seizure-related aspect comprises a cognitive or behavioral domain selected from the group consisting of communication, daily living skills, socialization and motor skills, and / or wherein the non-seizure-related aspect comprises a cognitive or behavioral subdomain selected from the group consisting of receptive communication, expressive communication, writing skills, personal skills, domestic skills, community skills, interpersonal relationships, play and leisure, coping skills, gross motor skills, and fine motor skills; wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses independently contains the compound at an amount of from about 25 to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, and a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the second loading dose, and wherein each maintenance dose after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0263] Provided herein, in some aspects, is a method of improving a non-seizure-related aspect in ahuman subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, thereby improving a non-seizure-related aspect in the human subject, wherein the non-seizure-related aspect comprises a cognitive or behavioral domain selected from the group consisting of communication, daily living skills, socialization and motor skills, and / or wherein the non-seizure-related aspect comprises a cognitive or behavioral subdomain selected from the group consisting of receptive communication, expressive communication, writing skills, personal skills, domestic skills, community skills, interpersonal relationships, play and leisure, coping skills, gross motor skills, and fine motor skills; wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses independently contains the compound at an amount of from about 25 to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, the third loading dose is administered from 2 weeks to 12 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the third loading dose, and wherein each maintenance after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601

[0264] In some embodiments, the cognitive or behavioral aspect is determined according to astandardized assessment.

[0265] In some embodiments, the standardized assessment comprises a Vineland Adaptive BehaviorScale, Third Edition (VABS-III); a Clinical Global Impression of Change (CGI-C); or a Caregiver Global Impression of Change (CaGI-C); or any combination thereof.

[0266] In some embodiments, (i) the standardized assessment comprises VABS-III and the improvementis a positive change in a Gross Scale Value (GSV); (ii) the standardized assessment comprises CGI-C and the improvement is a CGI-C score of 3, 2, or 1; or (iii) standardized assessment comprises CaGI-C and the improvement is a CaGI-C score of 3, 2, or 1.

[0267] In some embodiments, the standardized assessment comprises VABS-III and the positive changein GSV is at least 0.7000, 0.8000, 0.9000, 1.000, 1.250, 1.500, 1.750, 2.000, 2.250, 2.500, 2.750, 3.000, 3.250, 3.500, 3.750, 4.000, 4.250, 4.500, 4.750, 5.000, 5.250, 5.500, 5.750, 6.000, 7.000, 8.000, or 9.000.

[0268] In some embodiments, the standardized assessment comprises CGI-C and the improvement is aCGI-C score of 2 or 1.

[0269] In some embodiments, the standardized assessment comprises CaGI-C and the improvement is aCaGI-C score of 2 or 1.

[0270] Provided herein, in some aspects, is a method of reducing seizure frequency, seizure intensity,and / or seizure duration in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I),WSGR Ref. No.: 47991-748.601 or a salt thereof, thereby reducing seizure frequency, seizure intensity, and / or seizure duration in the human subject, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses independently contains the compound at an amount of from about 25 to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, and a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the second loading dose, and wherein each maintenance dose after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.

[0271] Provided herein, in some aspects, is a method of reducing seizure frequency, seizure intensity,and / or seizure duration in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, thereby reducing seizure frequency, seizure intensity, and / or seizure duration in the human subject, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or moreWSGR Ref. No.: 47991-748.601 maintenance doses independently contains the compound at an amount of from about 25 to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, the third loading dose is administered from 2 weeks to 12 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the third loading dose, and wherein each maintenance after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.

[0272] Provided herein, in some aspects, is a method of treating or reducing the likelihood of developinga disease or condition characterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising: (1) obtaining a pharmaceutical composition that is a liquid composition comprising a compound in a diluent, wherein the compound is according to the following chemical structure:(I), or a salt thereof, and wherein the diluent comprises: (a) calcium chloride (CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) at a concentration of about 0.1 mM to about 50 mM; (b) magnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) at a concentration of about 0.1 mM to about 50 mM; (c) potassium chloride (KCl) at a concentration of about 0.1 mM to about 20 mM;WSGR Ref. No.: 47991-748.601 (d) sodium chloride (NaCl) at a concentration of about 25 mM to about 250 mM; and (e) water; and (2) administering to the human subject multiple doses of the pharmaceutical composition, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

[0273] In some embodiments, the obtaining comprises diluting a concentrate with the diluent up to oneweek prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof dissolved in the diluent. In some of these embodiments, the obtaining comprises diluting a concentrate with the diluent up to 3 days prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof dissolved in the diluent. In some of these embodiments, the obtaining comprises diluting a concentrate with the diluent up to 2 days prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof dissolved in the diluent. In some of these embodiments, the obtaining comprises diluting a concentrate with the diluent up to 24 hours prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof dissolved in the diluent. In some of these embodiments, the obtaining comprises diluting a concentrate with the diluent up to 5 hours prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof dissolved in the diluent. In some of these embodiments, the obtaining comprises diluting a concentrate with the diluent up to one hour prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof dissolved in the diluent. In some of these embodiments, the compound has the following structure:WSGR Ref. No.: 47991-748.601(II). In some of these embodiments, the pharmaceutical composition comprises the compound or a salt thereof at a concentration of about 3 mg / mL, about 4.5 mg / mL or about 7 mg / mL. In some of these embodiments, the concentrate comprises the compound or a salt thereof at a concentration of from about 20 mg / mL to about 200 mg / mL, from about 30 mg / mL to about 150 mg / mL, from about 40 mg / mL to about 120 mg / mL, from about 50 mg / mL to about 100 mg / mL, or from about 60 mg / mL to about 80 mg / mL. In some of these embodiments, the concentrate comprises the compound or a salt thereof at a concentration of about 33 mg / mL, about 45 mg / mL, or about 70 mg / mL. In some of these embodiments, the diluent lacks sodium phosphate. In some of these embodiments, the pharmaceutical composition comprises 1-2 mM CaCl2or CaCl2·2H2O. In some of these embodiments, the pharmaceutical composition comprises about 1.4 mM CaCl2or CaCl2·2H2O. In some of these embodiments, the pharmaceutical composition comprises 0.5-1.5 mM MgCl2or MgCl2·6H2O. In some of these embodiments, the pharmaceutical composition comprises about 0.79 mM MgCl2or MgCl2·6H2O. In some of these embodiments, the pharmaceutical composition comprises from about 1 mM to about 2 mM calcium chloride dihydrate. In some of these embodiments, the pharmaceutical composition comprises about 1.4 mM calcium chloride dihydrate. In some of these embodiments, the pharmaceutical composition comprises from about 0.6 mM to about 1 mM chloride hexahydrate. In some of these embodiments, the pharmaceutical composition comprises about 0.79 mM magnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O). In some of these embodiments, the pharmaceutical composition comprises from about 2 mM to about 5 mM potassium chloride. In some of these embodiments, the pharmaceutical composition comprises about 3 mM potassium chloride. In some of these embodiments, the pharmaceutical composition comprises from about 125 mM to 145 mM sodiumWSGR Ref. No.: 47991-748.601 chloride. In some of these embodiments, the pharmaceutical composition comprises about 130 mM sodium chloride. In some of these embodiments, the pharmaceutical composition comprises from about 140 mM to 160 mM sodium chloride. In some of these embodiments, the pharmaceutical composition comprises about 150 mM sodium chloride. In some of these embodiments, in the pharmaceutical composition: (i) the concentration of the compound is about 3 mg / mL, about 4.5 mg / mL or about 7 mg / mL; (ii) the concentration of calcium chloride (CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) is about 1.4 mM; (iii) the concentration of magnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) is about 0.79 mM; (iv) the concentration of potassium chloride is about 3 mM; and (v) the concentration of sodium chloride is about 150 mM. In some of these embodiments, the pharmaceutical composition comprises: (a) calcium ion (Ca2+) at a concentration of about 1.4 mM; (b) magnesium ion (Mg2+) at a concentration of about 0.79 mM; (c) potassium ion (K+) at a concentration of about 3 mM; (d) sodium ion (Na+) at a concentration of about 160 mM; (e) chloride ion (Cl-) at a concentration of about 160 mM; and (f) water. In some of these embodiments, the pharmaceutical composition lacks Na2HPO4and / or NaH2PO4. In some of these embodiments, the pharmaceutical composition lacks phosphate ion. In some of these embodiments, each dose of the pharmaceutical composition comprises 10 mL of the diluent. In some of these embodiments, the pharmaceutical composition is administered as a bolus injection. In some of these embodiments, the method or the dosing regimen comprises administering the pharmaceutical composition as a bolus injection over 1 to 60 minutes, 1 to 50 minutes, 1 to 40 minutes, 1 to 30 minutes, 1 to 20 minutes, 1 to 10 minutes, 1 to 5 minutes, or 1 to 3 minutes. In some of these embodiments, the pharmaceutical composition is administered by infusion with a delivery pump. In some of these embodiments, the pharmaceutical composition is administered by intrathecal injection. In some of these embodiments, each dose of the pharmaceutical composition comprises a diluent of a volume of 10 mL, and the diluent is a solution that lacks sodium phosphate. In some of these embodiments, the pharmaceutical composition does not comprise a preservative. In certain embodiments, any method described herein treats or reduces the likelihood of developing the disease or condition in the human subject. INCORPORATION BY REFERENCE

[0274] All publications, patents, and patent applications mentioned in this specification are hereinincorporated by reference to the same extent as if each individual publication, patent, or patent application is specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0275] The features of the present disclosure are set forth with particularity in the appended claims. Abetter understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which:

[0276] FIGS. 1A-1B depict a schematic representation of a target pre-mRNA that contains a nonsense-mediated RNA decay-inducing exon (NMD exon mRNA) and therapeutic agent-mediated exclusion ofWSGR Ref. No.: 47991-748.601 the nonsense-mediated mRNA decay-inducing exon from the pre-mRNA to increase expression of the full-length target protein or functional RNA. FIG.1A shows a cell divided into nuclear and cytoplasmic compartments. In the nucleus, a pre-mRNA transcript of a target gene undergoes splicing to generate processed mRNA, and this processed mRNA is exported to the cytoplasm and translated into target protein. For this target gene, some fraction of the processed mRNA contains a nonsense-mediated mRNA decay-inducing exon (NMD exon mRNA) that is degraded in the cytoplasm, thus leading to no target protein production. FIG.1B shows an example of the same cell divided into nuclear and cytoplasmic compartments. Treatment with a therapeutic agent, such as an antisense oligomer (ASO), promotes the exclusion of the nonsense-mediated mRNA decay-inducing exon from the pre-mRNA and results in an increase in processed mRNA, which is in turn translated into higher levels of target protein.

[0277] FIG. 1C is a schematic representation of therapeutic ASO-mediated exclusion of a nonsense-mediated mRNA decay-inducing exon from a pre-mRNA, which decreases non-productive processed mRNA (e.g., with an NMD exon) and increases productive mRNA (e.g., without an NMD exon) and increases expression of the full-length target protein from the productive mRNA.

[0278] FIG. 1D shows identification of an exemplary sequence in the SCN1A gene that encodes anonsense-mediated mRNA decay (NMD)-inducing exon. The identification of the sequence in the SCN1A gene that encodes the NMD-inducing exon using comparative genomics is shown, visualized in the UCSC genome browser. The upper panel shows a graphic representation of the SCN1A gene to scale. The conservation level across 100 vertebrate species is shown as peaks. The highest peaks correspond to exons (black boxes), while no peaks are observed for the majority of the introns (lines with arrow heads). Peaks of conservation were identified in intron 20 (NM_006920), shown in the middle panel. Inspection of the conserved sequences identified an exon-like sequence of 64 bp (bottom panel, sequence highlighted in grey) flanked by 3′ and 5′ splice sites (underlined sequence). Inclusion of this exon leads to a frameshift and the introduction of a premature termination codon in exon 21 rendering the transcript a target of NMD.

[0279] FIG. 2 shows a study design timeline for monitoring wild type (WT) and Dravet Syndrome (DS)mice as well as a Kaplan-Meier curve showing DS and WT littermate mice monitored to 14 weeks for survival.

[0280] FIG. 3 shows an experimental design for the EEG seizure monitoring study in DS mice and theirWT littermates.

[0281] FIGS. 4A-4E show the results of monitoring seizures in mice administered with ASO-22(sequence set forth in SEQ ID NO: 42) or phosphate buffered saline (PBS). FIG.4A shows exemplary EEG recordings in DS mice. FIG.4B shows the number of seizures occurring in various regions of the brain in the two mice groups. *Indicates p<0.05. FIG.4C summarizes the total number of spontaneous seizures (generalized and focal) recorded between Postnatal Day 22 (P22) and Postnatal Day 46 (P46) in DS mice dosed with PBS (n=21) or ASO-22 (n=21). *Indicates p<0.05. FIG.4D shows the number of mice that had a number of seizures in each group. FIG.4E shows the effect of ASO-22 on the latency to the first recorded seizure between P22 and P46 in DS mice dosed with PBS (n=21) or ASO-22 (n=21).WSGR Ref. No.: 47991-748.601

[0282] FIGS. 5A-5G show that a single ICV injection of 20 µg ASO-22 at P2 results in reduced suddenunexpected death in epilepsy (SUDEP) incidence and increased NaV1.1 protein expression in DS mice. FIG.5A is a schematic for the experimental design. FIGS.5B, 5C, 5D, 5E, 5F, and 5G illustrate the ASO-22 exposure, fold change in Scn1a gene expression, and NaV1.1 expression in brain tissues at 7 weeks (FIGS.5B-5D) or 14 weeks (FIGS.5E-5G) after a single ICV injection of ASO-22 (20 μg) or PBS at P2.

[0283] FIGS. 6A-6B show the percent survival of DS and WT mice after a single ICV injection ofASO-22 (60 μg) or PBS on P14. FIG.6A is a schematic showing the study design. FIG.6B is a line chart showing the percent survival (y-axis) of the mice in various conditions (wild-type mice treated with PBS; wild-type mice treated with ASO-22; Scn1a+ / -mice treated with ASO-22; and Scn1a+ / -mice treated with PBS) over the course of days (x-axis).

[0284] FIGS. 7A-7F show the ASO-22 exposure, Scn1a expression, and NaV1.1 expression in braintissues at P35 (FIGS. 7A-7C) and P90 (FIGS.7D-7F) after a single ICV injection of ASO-22 (60 μg) or PBS on P14. FIG.7A illustrates the concentration of ASO-22 in brain tissue (μg / g), FIG.7B shows the fold change of Scn1a gene expression, and FIG.7C shows the NaV1.1 expression relative to adult brain tissue at P35 for wild-type and Scn1a+ / -mice after ICV injection with either ASO-22 (60 μg) or PBS on P14. FIG.7D illustrates the concentration of ASO-22 in brain tissue (μg / g), FIG.7E shows the fold change of Scn1a gene expression, and FIG.7F shows the NaV1.1 expression relative to adult brain tissue at P90 for wild-type and Scn1a+ / -mice after ICV injection with either ASO-22 (60 μg) or PBS on P14.

[0285] FIG. 8 shows the experimental conditions and numbers of monkeys used per group.

[0286] FIGS. 9A-9B show the levels of ASO-22 in the cynomolgus monkey brain on study day 3 (FIG.9A) and day 29 (FIG.9B).

[0287] FIGS. 10A-10B show the levels of NaV1.1 protein in cynomolgus monkey brain regions on studyday 3 (FIG.10A) and day 29 (FIG.10B).

[0288] FIGS. 11A-11B show the percentages of productive SCN1A gene to total SCN1A gene as anevaluation of target engagement in cynomolgus monkeys on study day 3 (FIG.11A) and day 29 (FIG. 11B).

[0289] FIG. 12A shows the plasma pharmacokinetics in cynomolgus monkey after IntrathecalAdministration of ASO-22. FIG.12B shows the levels of ASO-22 in the cynomolgus monkey cerebrospinal fluid (CSF) on study day 3 and 29.

[0290] FIGS. 13A-13D depict identification of an alternative splicing event in SCN1A that results inNMD. FIG. 13A shows SCN1A splicing isoforms with or without inclusion of the alternative exon inReNcells as demonstrated by RT-PCR. FIG.13B shows results from an evaluation of the alternative splice event of the SCN1A gene in the cerebral cortex from 4 species. FIG.13C shows an image of a TBE PAGE gel of RT-PCR products corresponding to Scn1a productive (lower bands, 498 bp) and non- productive transcript (upper bands, 562 bp) amplified from total RNA extracted from WT C57BL / 6J mouse brains from P0 to P20 and at 10 months. Mouse Gapdh was used as a loading control. FIG.13DWSGR Ref. No.: 47991-748.601 summarizes expression of Scn1a productive and non-productive transcript in postnatal mouse brains, calculated with optical densities of PCR products shown in FIG.13C.

[0291] FIGS. 14A-14E depict that selected ASOs suppressed the NMD splicing event and increased theexpression of productive SCN1A mRNA in ReNcells. FIG.14A is an exemplary TBE PAGE gel image of RT-PCR products corresponding to SCN1A productive (lower bands, 549 bp) and non-productive mRNA containing exon 20X (upper bands, 613 bp) in ReNcells after gymnotic (free) uptake of ASO. FIG.14B is a histogram showing the percentage of Exon 20X inclusion (y-axis) after treatment with various ASOs (x-axis). FIG.14C is a histogram showing the fold change in Scn1a gene expression (y- axis) after treatment with various ASOs (x-axis). FIG.14D is a graph illustrating the fold change in Scn1a gene expression (y-axis) after treatment with ASO-22 at various concentrations in nM (x-axis) by free uptake or nucleofection. FIG.14E is a histogram showing the fold change in Scn1a gene expression (y-axis) after treatment with either a non-targeting ASO (NT) or ASO-22, each at various concentrations (20 µM, 8 µM, 3 µM) (x-axis).

[0292] FIGS. 15A-15C show dose-dependent effects of ASO-22 on splicing and expression of SCN1AmRNA in ReNcells. FIG.15A shows an exemplary TBE PAGE gel image of RT-PCR products corresponding to SCN1A productive mRNA (lower bands, 549 bp) and non-productive mRNA containing exon 20X (upper bands, 613 bp) in ReNcells. RPL32 was used as the loading control. FIG.15B is a histogram showing the fold change in SCN1A productive mRNA after treatment with various controls (sham, sham with cycloheximide, non-targeting (NT) ASO, or NT ASO with cycloheximide), ASO-22 at various concentrations (20 µM, 8 µM, 3 µM), or ASO-22 with cycloheximide at various concentrations (20 µM, 8 µM, 3 µM) as indicated on the x-axis. FIG.15C is a histogram showing the fold change in SCN1A non-productive mRNA after treatment with various controls (sham, sham with cycloheximide, non-targeting (NT) ASO, or NT ASO with cycloheximide), ASO-22 at various concentrations (20 µM, 8 µM, 3 µM), or ASO-22 with cycloheximide at various concentrations (20 µM, 8 µM, 3 µM) as indicated on the x-axis.

[0293] FIGS. 16A-16H show that ASO-22 ICV injection causes dose-dependent and durable increasesin Scn1a mRNA and NaV1.1 protein expression in mouse brain. FIG.16A is a schematic illustrating the experimental study design for ASO-22. FIG.16B is a graph showing the percentage of Exon 21X inclusion (amount of non-productive Scn1a transcript) after a single ICV injection of ASO-22 at 0.3, 1, 3, 5, 10, 20 or 30 µg (x-axis). FIG.16C is a graph showing the fold change in mRNA (amount of productive Scn1a transcript) after a single ICV injection of ASO-22 at 0.3, 1, 3, 5, 10, 20 or 30 µg (x- axis). FIG.16D is a graph showing the percentage of NaV1.1 protein expression relative to adult brain tissue after a single ICV injection of ASO-22 at 0.3, 1, 3, 5, 10, 20 or 30 µg (x-axis). FIG.16E is a histogram showing the effect of ASO-22 (fold change in mRNA) on expression of the 9 VGSC α subunit genes in mouse brain. Expression of Scn1a productive transcript and the remaining 8 VGSC α subunit genes plus Nax (Scn7a) in mouse brains following ICV injection of PBS, a non-target ASO control (NT, 20 μg) or different doses of ASO-22 was measured by probe-based qPCR. Expression of each transcript was first normalized to endogenous Gapdh then compared to PBS injection controls. FIG.16F is aWSGR Ref. No.: 47991-748.601 schematic of the experimental study design used to determine the durability of the ASO-22 effect in brain. FIG.16G shows the relative expression of productive Scn1a transcript (y-axis) after treatment with ASO-22 or PBS over the course of days (x-axis). FIG.16H shows the percentage of NaV1.1 protein expression relative to adult brain tissue (y-axis) after treatment with ASO-22 or PBS over the course of days (x-axis).

[0294] FIG. 17 shows dose-dependent effects of ASO-22 on the expression of Scn1a mRNA in ICV-injected neonatal mouse brains (§ = nonproductive; * = productive).

[0295] FIG. 18 shows dose-dependent effects of ASO-22 on the expression of NaV1.1 in ICV-injectedneonatal mouse brains.

[0296] FIG. 19 shows expression of Scn1a mRNA in mouse brains at different post-injection days (§ =nonproductive; * = productive).

[0297] FIG. 20 shows expression of NaV1.1 in mouse brains at different post-injection days.

[0298] FIG. 21 shows validation of the two anti-NaV1.1 antibodies used in the Examples. Specificity ofthe two anti-NaV1.1 antibodies, Alomone ASC-001 and NeuroMab 75-023, was tested using total protein prepared from a Scn1a- / -mouse brain (middle lane) and brains of two WT littermates (left and right lanes).

[0299] FIG. 22 shows a schematic representation of clinical manifestations of Dravet Syndrome andtheir relative incidences according to age. AA: atypical absences; AE: acute encephalopathy; CG: crouching gait; CPS: complex partial seizures; DD: developmental delay; DS: Dravet syndrome; EEG: electroencephalogram; FSz: complex febrile seizures; GMS: generalized motor seizures; HS: hyperthermia sensitivity; m: month; MSz: myoclonic seizures; OS: obtundation status; SE: status epilepticus; SUDEP: sudden unexpected death in epilepsy; y: years; * Moderate fever for 60%, mostly clonic generalized and unilateral motor seizures; ** Difficult to distinguish between AA and CPS without ictal EEG recording, so their precise incidence is unknown. See, e.g., Gataullina and Dulac, 2017, of which the entire content is incorporated herein by reference.

[0300] FIG. 23 shows TANGO (Targeted Augmentation of Nuclear Gene Output) that may be used totreat Dravet syndrome.

[0301] FIG. 24 shows the transformative potential of TANGO technology in Dravet syndrome.

[0302] FIG. 25 shows the study design. Phase 1 / 2a open-label, 2-part study conducted at approximately20 sites in the United States.

[0303] FIG. 26 shows a schematic representation of the study design.

[0304] FIG. 27 shows patient inclusion and exclusion criteria.

[0305] FIG. 28 shows study assessments.

[0306] FIG. 29 shows the workflow of a Phase 1 / 2a study of Compound-A.

[0307] FIG. 30 shows two plots summarizing cerebrospinal fluid (CSF) exposure of Compound-A insingle ascending dose (SAD) cohorts and multiple ascending dose (MAD) cohorts, respectively.

[0308] FIGS. 31A-31B show two plots summarizing median percent change in seizure frequency frombaseline level to the period between Day 29 and 84 post administration of Compound-A (in reference toWSGR Ref. No.: 47991-748.601 1stdose, Day 29-84) in 2- to 12-year-old subjects (FIG.31A) and 13- to 18-year-old (FIG.31B), all combined by cohort.

[0309] FIGS. 32A-32B show two plots summarizing median percent change in seizure frequency frombaseline in patients of all ages as combined by cohort in the period between Day 1 and Day 84 (Day 1- 84) post administration (FIG.32A), and in the period between Day 29-84 (Day 29-84) post administration (FIG.32B).

[0310] FIGS. 33A-33C show the study design for the Phase 1 / 2a clinical trials for ASO-1. FIG. 33Ashows the study design and dosing schedule using the Single Ascending Dose (SAD) regime (MONARCH) before patients can become eligible to enroll in the LONGWING OLE. FIG.33B shows the study design and dosing schedule using the Multiple Ascending Dose regime (MONARCH) before patients can become eligible to enroll in the LONGWING OLE. FIG.33C shows the study design and dosing schedule using the Multiple Ascending Dose regime (ADMIRAL) before patients can become eligible to enroll in the LONGWING OLE.

[0311] FIG. 34 shows a plot summarizing median percent change in seizure frequency from baseline inpatients of all ages receiving 30 mg, 45 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 225 post administration in the MONARCH study and the mean percent change in seizure frequency from baseline in patients of all ages receiving 30 mg, 45 mg, or 70 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 225 post administration in the ADMIRAL study.

[0312] FIG. 35 shows a plot summarizing median percent change in seizure frequency from baseline inpatients of all ages receiving 30 mg or 45 mg of ASO-1 as combined by cohort in the period between Day 29 and Day 85 post administration in the MONARCH study and the mean percent change in seizure frequency from baseline in patients of all ages receiving 30 mg, 45 mg, or 70 mg of ASO-1 as combined by cohort in the period between Day 29 and Day 87 post administration in the ADMIRAL study.

[0313] FIGS. 36A-36B show plots summarizing mean percent change in seizure frequency frombaseline in patients between ages 2-12 and between ages 13-18 years receiving 30 mg or 45 mg of ASO- 1 as combined by cohort in the period between Day 1 and Day 225 post administration in the MONARCH study. FIG.36A shows a plot summarizing mean percent change in seizure frequency from baseline in patients between ages 2-12 and between ages 13-18 years receiving 30 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 225 post administration in the MONARCH study. FIG.36B shows a plot summarizing mean percent change in seizure frequency from baseline in patients between ages 2-12 and between ages 13-18 years receiving 45 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 225 post administration in the MONARCH study.

[0314] FIGS. 37A-37C show plots summarizing mean percent change in seizure frequency frombaseline in patients between ages 2-12 and between ages 13-18 years receiving 30 mg, 45 mg, or 70 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 252 post administration in the ADMIRAL study. FIG. 37A shows a plot summarizing mean percent change in seizure frequency from baseline in patients between ages 2-12 and between ages 13-18 years receiving 30 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 252 post administration in the ADMIRALWSGR Ref. No.: 47991-748.601 study. FIG.37B shows a plot summarizing mean percent change in seizure frequency from baseline in patients between ages 2-12 and between ages 13-18 years receiving 45 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 252 post administration in the ADMIRAL study. FIG. 37Cshows a plot summarizing mean percent change in seizure frequency from baseline in patients between ages 2-12 and between ages 13-18 years receiving 70 mg of ASO-1 as combined by cohort in the period between Day 1 and Day 252 post administration in the ADMIRAL study.

[0315] FIG. 38 shows a plot summarizing mean percent change in seizure frequency from baseline inpatients between ages 2-12 and between ages 13-18 years receiving 2 or 3 doses of 70 mg of ASO-1, as combined by cohort in the period between Day 1 and Day 252 post administration in the ADMIRAL study.

[0316] FIGS. 39A-39B show plots summarizing mean percent change in seizure frequency frombaseline in all patients receiving 30 mg, 45 mg, or 70 mg of ASO-1, as analyzed 3 or 6 months post last dose administration. FIG.39A shows a plot summarizing mean percent change in seizure frequency from baseline in all patients receiving 30 mg, 45 mg, or 70 mg of ASO-1, as analyzed 3 months post last dose administration. FIG.39B shows a plot summarizing mean percent change in seizure frequency from baseline in all patients receiving 30 mg, 45 mg, or 70 mg of ASO-1, as analyzed 6 months post last dose administration.

[0317] FIGS. 40A-40B show plots summarizing mean percent change in seizure frequency frombaseline in all patients receiving 2 or 3 doses of 70 mg of ASO-1, as analyzed 3 or 6 months post last dose administration in the ADMIRAL study. FIG.40A shows a plot summarizing mean percent change in seizure frequency from baseline in all patients receiving 2 or 3 doses of 70 mg of ASO-1, as analyzed 3 months post last dose administration in the ADMIRAL study. FIG.40B shows a plot summarizing mean percent change in seizure frequency from baseline in all patients receiving 2 or 3 doses of 70 mg of ASO-1, as analyzed 6 months post last dose administration in the ADMIRAL study.

[0318] FIG. 41 shows a plot summarizing mean percent change in seizure frequency from baseline in allpatients receiving 30 mg or 45 mg of ASO-1 maintenance dose every 4 months in the OLE study.

[0319] FIGS. 42A-42B show plots showing improvement in receptive communication and expressivecommunication in patients receiving ASO-1 for over one year of dosing compared to observed natural history of the disease measured on the Vineland (VABS-III) scale. FIG.42A shows a plot showing improvement in receptive communication in patients receiving ASO-1 for over one year of dosing compared to observed natural history of the disease measured on the Vineland (VABS-III) scale. FIG. 42B shows a plot showing improvement in receptive communication in patients receiving ASO-1 for over one year of dosing compared to observed natural history of the disease measured on the Vineland (VABS-III) scale.

[0320] FIG. 43 shows a plot showing improvement in gross motor skills in patients receiving ASO-1 forover one year of dosing compared to observed natural history of the disease measured on the Vineland (VABS-III) scale.WSGR Ref. No.: 47991-748.601

[0321] FIG. 44 shows a plot showing improvement in executive function in patients receiving ASO-1for over one year of dosing compared to observed natural history of the disease measured by Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) Global Executive Composite (GEC). A decrease in BRIEF-P score indicates an improvement in executive function.

[0322] FIGS. 45A-45B show plots showing improvement in clinical and caregiver impression of changein patients receiving ASO-1 for over one year of dosing compared to observed natural history of the disease measured on the Vineland (VABS-III) scale. FIG.45A shows a plot showing improvement in clinical impression of change in patients receiving ASO-1 for over one year of dosing compared to observed natural history of the disease measured on the Vineland (VABS-III) scale. FIG.45B shows a plot showing improvement in caregiver impression of change in patients receiving ASO-1 for over one year of dosing compared to observed natural history of the disease measured on the Vineland (VABS-III) scale. Measurements for Clinical Global Impression of Change (CGI-C) (FIG.45A) and Caregiver Global Impression of Change (CaGI-C) (FIG.45B) are recorded as scores on a 7-point scale, presented in Least Square (LS) means, shown with a 95% confidence interval (CI).

[0323] FIG. 46 is a line chart illustrating the median percentage change of convulsive seizure frequencyfrom baseline after two or three administrations of a dose of ASO (30 mg, 45 mg, or 70 mg) over time measured in days after the first administration. The dotted line is the baseline, and data on this line indicates no change from baseline. Reductions in convulsive seizure frequency are represented by data points below the dotted line. The number of days elapsed since the first dosage administration are indicated on the x-axis (e.g., D1-28 represents day 1 to day 28 after the first loading dose the patient received).

[0324] FIGS. 47A-47D are data showing reductions in convulsive seizure frequency from baseline afteradministration of various doses of ASO-1. FIGS.47A-47C are histograms illustrating the median percentage change in convulsive seizure frequency at three months (FIG.47A), four months (FIG.47B), and six months (FIG.47C) after the administration of the last loading dose compared to baseline convulsive seizure frequency. Left columns in each histogram represent data from cohorts administered with one 70-mg loading dose (Single Ascending Dose, or SAD). Center columns represent data from the cohort that was administered with two loading doses, each at 70 mg (Multiple Administered Doses, or MAD – 2 doses). Right columns represent data from the cohort that was administered with three loading doses, each at 70 mg (Multiple Administered Doses, or MAD – 3 doses). Data were evaluated from eight participants in the SAD cohort (n=8), five participants in the MAD – 2 doses cohort (n=5), and five participants in the MAD – 3 doses cohort (n=5) at the three-month mark. Data were evaluated from eight participants in the SAD cohort (n=8), five participants in the MAD – 2 doses cohort (n=5), and four participants in the MAD – 3 doses cohort (n=4) at the four-month mark. Data were evaluated from seven participants in the SAD cohort (n=7), five participants in the MAD – 2 doses cohort (n=5), and four participants in the MAD – 3 doses cohort (n=4) at the six-month mark. A reduction in convulsive seizure frequency from baseline corresponds to a negative percentage. FIG.47D is a line chart showing the reductions in convulsive seizure frequency from baseline after MONARCH and ADMIRAL participantsWSGR Ref. No.: 47991-748.601 were administered either 1, 2, or 3 doses of 70 mg ASO-1. ASO-1 was administered on Days 1, 29 and 57 in MONARCH, and on Days 1, 57 and 85 in ADMIRAL. MONARCH ended at Day 225 and ADMIRAL ended at Day 253. D represents “day.”

[0325] FIGS. 48A-48B are histograms illustrating the median percentage change in convulsive seizurefrequency at three, four, and six months after the administration of the last loading dose of a single 70-mg dose (FIG.48A), or the last loading dose of multiple 70-mg doses (FIG. 48B) compared to baseline convulsive seizure frequency. Left columns in each histogram represent data from three months after administration of the last loading dose for a single 70-mg dose (FIG.48A, left column), or multiple 70- mg doses (FIG.48B, left column). Center columns in each histogram represent data from four months after administration of the last loading dose for a single 70-mg dose (FIG.48A, center column), or multiple 70-mg doses (FIG.48B, center column). Right columns in each histogram represent data from six months after administration of the last loading dose for a single 70-mg dose (FIG.48A, right column), or multiple 70-mg doses (FIG.48B, right column). Data were evaluated in the single 70-mg loading dose condition from eight participants (n=8) at the third month after loading dose injection, eight participants (n=8) at the fourth month, and seven (n=7) participants at the sixth month. Data were evaluated in the multiple 70-mg loading dose condition from ten participants (n=10) at the third month after the last loading dose injection, ten participants (n=10) at the fourth month, and nine participants (n=9) at the sixth month. A reduction in convulsive seizure frequency from baseline corresponds to a negative percentage.

[0326] FIGS. 49A-49B are bar charts showing the percentage change in convulsive seizure frequency(CSF) compared to baseline seizure frequency. FIG.49A shows CSF data at 3 months, and FIG.49B shows CSF data at 6 months after the last 70-mg dose for participants who were administered one, two, or three 70-mg doses. A reduction in seizure frequency is denoted as a negative percentage value. Bars that extend past the dotted line indicate a greater than 50% reduction in convulsive seizures. Each bar represents the data of a single patient, with the age of the patient located immediately below the bar.

[0327] FIG. 49C is a bar chart of data for Clinical Global Impression of Change (CGI-C), and FIG.49D is a bar chart of data for Caregiver Global Impression of Change (CaGI-C), and both scales indicate improvements in the overall clinical status of patients who received single or multiple doses of 70 mg ASO-16 months after their last dose. The x-axis shows the possible scores* of the CGI-C and CaGI-C from Very Much Improved to Very Much Worse. The y-axis shows the number of patients. Percentages at the top of each bar represent the fraction of patients in each CGI-C and CaGI-C score. LS = “least- squares.” *CGI-C and CaGI-C assessments are scored on a Likert scale with seven response options: 1 (Very much improved), 2 (Much improved), 3 (Minimally improved), 4 (No change), 5 (Minimally worse), 6 (Much worse), or 7 (Very much worse). Sample size, N=63 for both assessments. Phase 1 / 2a data-cut was December 12, 2023 (after End of Study). †Mixed-effects model for repeated measures constructed with data from Phase 1 / 2a studies. One patient who received an incorrect dose and three patients with <4 seizures during baseline were excluded. Patients’ quality of life (QoL) was improved as demonstrated by model outcomes for the EQ-VAS component of the EQ-5D-Y assessment.WSGR Ref. No.: 47991-748.601

[0328] FIGS. 50A-50C illustrate the median percentage change in convulsive seizure frequency (CSF)in the SWALLOWTAIL / LONGWING OLE studies. FIG.50A is a line chart of the median percentage change in convulsive seizure frequency from the Phase 1 / 2 study’s baseline seizure frequency over time (in weeks, x-axis) when ASO is administered at regular intervals, represented by “ASO-1” rectangles. Square data points represent data combined from the SWALLOWTAIL / LONGWING open-label extension (OLE) studies in which patients were administered either 30- or 45-mg doses at regular intervals (at weeks 1-4, weeks 17-20, and weeks 33-36). Triangular data points represent data from patients who had received three 70-mg doses from the Phase 1 / 2 study, after which 24 weeks had elapsed since the last dose, and a 45-mg maintenance dose was administered in the OLE studies. FIG.50B is a line chart of the median percentage change in convulsive seizure frequency from the Phase 1 / 2 study’s baseline seizure frequency over time (in months, x-axis) when ASO is administered at regular intervals of approximately every four months as indicated by the arrows in the axis, where the first dose is administered at the start of month 1, the second dose is administered at approximately the end of month 4, the third dose is administered at approximately the end of month 8, the fourth dose is administered at approximately the end of month 12, etc. Triangular data points represent data for participants who received one, two, or three 70-mg doses of ASO-1 in the MONARCH / ADMIRAL Phase 1 / 2a studies, followed by 30-mg or 45-mg maintenance doses of ASO-1 during the SWALLOWTAIL / LONGWING OLE studies over the course of 24 months. FIG.50C is a line chart of the median percentage change in convulsive seizure frequency from the Phase 1 / 2 study’s baseline seizure frequency over the course of 8 months. Participants who received one 70-mg dose in the MONARCH Phase 1 / 2a study, followed by 30- mg maintenance doses in the SWALLOWTAIL OLE study, are represented by light gray diamond data points. Participants who received two 70-mg doses in the ADMIRAL Phase 1 / 2a study, followed by 45- mg maintenance doses in the LONGWING OLE study, are represented by square data points. Participants who received three 70-mg doses in the ADMIRAL Phase 1 / 2a study, followed by 45-mg maintenance doses in the LONGWING OLE study, are represented by dark gray diamond data points.

[0329] FIG. 51 is a schematic illustrating the four main domains (communication, daily living skills,socialization, and motor skills) and eleven subdomains of cognition and behavior evaluated in a Vineland Adaptive Behavior Scale (VABS-III). Highlighted subdomains were selected for further analysis. Dravet Syndrome (DS) patients experience floor effects in other subdomains.

[0330] FIG. 52 is a chart showing the change in Growth Scale Value (GSV) (x-axis) for variouscognitive and behavioral skills in ADMIRAL participants as assessed by Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). Bars to the right of the 0 mark (positive direction) indicate improvement in a specified behavior, while bars to the left of the 0 mark (negative direction) indicate worsening of a specified behavior. Eighteen ADMIRAL Phase 1 / 2 study patients were evaluated at the initial screen, and seventeen were evaluated at week 36.

[0331] FIGS. 53A-53B are bar charts showing Clinical Global Impression of Change (CGI-C) (FIG.53A) and Caregiver Global Impression of Change (CaGI-C) (FIG.53B) measurements recorded as scores on a 7-point scale, presented in Least Square (LS) means, shown with a 95% confidence intervalWSGR Ref. No.: 47991-748.601 (CI). The BUTTERFLY natural history scores were used as the baseline reference scores (dotted line). MONARCH / ADMIRAL scores for both CGI-C and CaGI-C were lower than each of the reference BUTTERFLY scores, indicating improvement in patient condition after treatment with at least a 30-mg dose of ASO.

[0332] FIGS. 54A-54B are histograms illustrating the results of Vineland-3 for expressivecommunication (FIG.54A) and receptive communication (FIG.54B) for participants of the BUTTERFLY natural history study (FIGS.54A-54B, left columns) and ADMIRAL Phase 1 / 2 study (FIGS.54A-54B, right columns) at the end of 36 weeks. Improvement corresponds to a positive change in Growth Scale Value (GSV), and worsening corresponds to a negative change in GSV. At week 36 (or month 9), participants of the BUTTERLY natural history study had a change in GSV of 0.118 in expressive communication and -3.148 in receptive communication; participants of the ADMIRAL Phase 1 / 2 study had a change in GSV of 3.222 in expressive communication and 6.250 in receptive communication.

[0333] FIGS. 55A-55B are histograms illustrating the results of Vineland-3 for personal skills (FIG.55A) and interpersonal skills (FIG.55B) for participants of the BUTTERFLY natural history study (FIGS.55A-55B, left columns) and ADMIRAL Phase 1 / 2 study (FIGS.55A-55B, right columns) at the end of 36 weeks. Improvement corresponds to a positive change in Growth Scale Value (GSV), and worsening corresponds to a negative change in GSV. At week 36 (or month 9), participants of the BUTTERLY natural history study had a change in GSV of 0.484 in personal skills and -1.434 in interpersonal relationships skills; participants of the ADMIRAL Phase 1 / 2 study had a change in GSV of 1.855 in personal skills and 4.407 in interpersonal skills.

[0334] FIGS. 56A-56C are charts showing the change in Growth Scale Value (GSV) (x-axis) forvarious cognitive and behavioral skills in SWALLOWTAIL and LONGWING participants as assessed by Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). Bars to the right of the 0 mark (positive direction) indicate improvement in a specified behavior, while bars to the left of the 0 mark (negative direction) indicate worsening of a specified behavior. SWALLOWTAIL and LONGWING participants were treated at regular time intervals with either 30- or 45-mg doses of ASO and evaluated at month 12 (FIG.56A) and month 24 (FIG.56B). FIG. 56C is a summative chart comparing the Vineland-3 data at month 12 (light gray bars) and month 24 (dark gray bars). Change in GSV is measured using the OLE study as the baseline.

[0335] FIGS. 57A-57B are histograms showing change in GSV over time for expressivecommunication (FIG.57A) and receptive communication (FIG.57B) in the BUTTERFLY natural history study and SWALLOWTAIL / LONGWING studies. Improvements in behavior correspond to a positive change in GSV (bars above line demarcated by 0), and worsened behavior correspond to a negative change in GSV (bars below line demarcated by 0). SWALLOWTAIL / LONGWING study participants were observed to have positive changes in GSV for both expressive and receptive communication over the course of 12 months. BUTTERFLY natural history participants had nearly negligible positive change in GSV in expressive communication and worsening of receptiveWSGR Ref. No.: 47991-748.601 communication over the course of 12 months. At month 4, expressive communication in the natural history study had a change in GSV of 0.054 and receptive communication had a change in GSV of - 2.166, while expressive communication in the SWALLOWTAIL / LONGWING studies had a change in GSV of 0.185 and receptive communication had a change in GSV of 1.623. At month 8, expressive communication in the natural history study had a change in GSV of 0.105 and receptive communication had a change in GSV of -2.951, while expressive communication in the SWALLOWTAIL / LONGWING studies had a change in GSV of 1.209 and receptive communication had a change in GSV of 2.337. At month 12, expressive communication in the natural history study had a change in GSV of 0.171 and receptive communication had a change in GSV of -3.934, while expressive communication in the SWALLOWTAIL / LONGWING studies had a change in GSV of 2.490 and receptive communication had a change in GSV of 3.231.

[0336] FIGS. 58A-58B are histograms showing change in GSV over time for personal skills (FIG. 58A)and interpersonal relationship skills (FIG.58B) in the BUTTERFLY natural history study and SWALLOWTAIL / LONGWING studies. Improvements in behavior correspond to a positive change in GSV (bars above line demarcated by 0), and worsened behavior correspond to a negative change in GSV (bars below line demarcated by 0). SWALLOWTAIL / LONGWING study participants were observed to have positive changes in GSV for both expressive and interpersonal skills over the course of 12 months. BUTTERFLY natural history participants had nearly negligible positive change in GSV in personal skills and slight improvement of interpersonal relationship skills over the course of 12 months. At month 4, personal skills in the natural history study had a change in GSV of 0.408 and interpersonal skills had a change in GSV of -2.629, while interpersonal skills in the SWALLOWTAIL / LONGWING studies had a change in GSV of 1.276. At month 8, personal skills in the natural history study had a change in GSV of 0.469 and interpersonal skills had a change in GSV of -1.673, while personal skills in the SWALLOWTAIL / LONGWING studies had a change in GSV of 1.687 and interpersonal skills had a change in GSV of 2.389. At month 12, personal skills in the natural history study had a change in GSV of 0.530 and interpersonal skills had a change in GSV of -0.478, while personal skills in the SWALLOWTAIL / LONGWING studies had a change in GSV of 2.970 and interpersonal skills had a change in GSV of 3.780.

[0337] FIGS. 59A-59D are bar charts showing Clinical Global Impression of Change (CGI-C) andCaregiver Global Impression of Change (CaGI-C) for SWALLOWTAIL and LONGWING participants administered maintenance doses of 30 mg or 45 mg of ASO-1. FIG.59A shows CGI-C data and FIG. 59B shows CaGI-C data at 4, 8, and 12 months (x-axis) with the least-squares means values (y-axis) for both BUTTERFLY and SWALLOWTAIL / LONGWING participants. CGI-C and CaGI-C measurements were recorded as scores on a 7-point scale. Data are presented in Least Square (LS) means, shown with a 95% confidence interval (CI). The BUTTERFLY natural history scores were used as the baseline reference scores (dotted line). SWALLOWTAIL / LONGWING scores for both CGI-C and CaGI-C were lower than each of the reference BUTTERFLY scores, indicating improvement in patient condition after treatment with either a 30- or 45-mg dose of ASO. FIG.59C shows CGI-C data at 24 months and FIG.WSGR Ref. No.: 47991-748.601 59D shows CaGI-C data at 24 months for SWALLOWTAIL / LONGWING OLE participants, with both scales indicating substantial and ongoing improvements in overall clinical status through Month 24 of the OLEs. The x-axis shows the possible scores* of the CGI-C and CaGI-C from Very Much Improved to Very Much Worse. The y-axis shows the number of patients. Percentages at the top of each bar represent the fraction of patients in each CGI-C and CaGI-C parameter. LS = “Least-Squares.” *CGI-C and CaGI- C assessments are scored on a Likert scale with seven response options: 1 (Very much improved), 2 (Much improved), 3 (Minimally improved), 4 (No change), 5 (Minimally worse), 6 (Much worse), or 7 (Very much worse). †Mixed-effects model for repeated measures constructed using data through Month 24 (Week 96) from enrolled patients in OLE studies. One patient who received an incorrect dose in Phase 1 / 2a study was excluded. SWALLOWTAIL / LONGWING sample sizes: n=70 at Week 16, n=50 (CGI-C) and 51 (CaGI-C) at Week 48, n=22 at Week 96. OLE data-cut: June 28, 2024.

[0338] FIGS. 60A-60B are line charts of Exposure-Response (ER) seizure models produced when twoloading doses of 70 mg ASO are followed by 70-mg maintenance doses administered at regular time intervals (FIG.60A) and when three loading doses of 70 mg followed by 70-mg maintenance doses administered at regular intervals (FIG.60B). Predicted median percentage change in convulsive seizure frequency (y-axis) is plotted against time in weeks (x-axis). Arrows with “70” at the top of the charts indicate the time points during which 70-mg doses of ASO would be administered. The model based on two 70-mg loading doses, followed by four 70-mg maintenance doses, estimates that there would be a - 65% reduction in seizure frequency by four months after the 4thmaintenance dose. The model based on three 70-mg loading doses, followed by four 70-mg maintenance doses, estimates that there would be a - 67% reduction in seizure frequency by four months after the 4thmaintenance dose.

[0339] FIGS. 61A-61B are graphs generated from a PK model used to predict when the brain wouldachieve a steady state of 26.0 µg ASO drug per gram of brain weight sans thalamus when a patient is administered either two 70-mg loading doses followed by four 70-mg maintenance doses (FIG.61A), or three 70-mg loading doses followed by four 70-mg maintenance doses (FIG.61B). Concentration as µg ASO drug per gram of mean brain weight sans thalamus (µg / g) (y-axis) is plotted against time in days (x- axis). The number 70 indicates the timepoints at which 70 mg of ASO would be administered. The arrows at the tops of the graphs indicate the predicted time at which the brain achieves the 26.0 µg / g steady state.

[0340] FIGS. 62A-62B are line charts of Exposure-Response (ER) seizure models produced when two70-mg loading doses are followed by four 70-mg maintenance doses administered at regular time intervals (FIG.62A) and when two 70-mg loading doses are followed by four 45-mg maintenance doses administered at regular time intervals (FIG.62B). Predicted median percentage change in convulsive seizure frequency (y-axis) is plotted against time in weeks (x-axis). Arrows with “70” or “45” at the top of the charts indicate the time points during which either 70-mg or 45-mg doses of ASO would be administered. The model based on two 70-mg loading doses, followed by four 70-mg maintenance doses, estimates that there would be a -65% reduction in seizure frequency by four months after the fourth maintenance dose. The model based on two 70-mg loading doses, followed by four 45-mg maintenanceWSGR Ref. No.: 47991-748.601 doses, estimates that there would be a -55% reduction in seizure frequency by four months after the fourth maintenance dose.

[0341] FIGS. 63A-63B are graphs generated from a PK model used to predict when the brain wouldachieve a steady state of a certain concentration comprising the eight of ASO drug in µg per gram of brain weight sans thalamus. A patient who is administered two 70-mg loading doses followed by four 70- mg maintenance doses was predicted to reach a 26.0 µg / g steady state by 2 months (FIG.63A), and a patient who is administered two 70-mg loading doses followed by four 45-mg maintenance doses was predicted to reach a 16.7 µg / g steady state by 10 months (FIG.63B). Concentration as µg ASO drug per gram of mean brain weight sans thalamus (µg / g) (y-axis) is plotted against time in days (x-axis). The numbers “70” and “45” indicate the timepoints at which either 70 mg or 45 mg of ASO would be administered. The arrows at the tops of the graphs indicate the predicted time at which the brain achieves a steady state.

[0342] FIG. 64 is a schematic illustrating the sequence of events scheduled to occur during the studyperiod of administering two 70-mg loading doses followed by 70-mg maintenance doses. The observation period is 6 weeks long; the initial treatment period is 24 weeks long; and the ongoing treatment period is 16 weeks long. Either a placebo or the ASO drug is administered at the time points marked by the corresponding icons (syringe icon = ASO drug; threaded needle icon = placebo).

[0343] FIG. 65 is a chart showing the change in Growth Scale Value (GSV) (x-axis) for variouscognitive and behavioral skills in BUTTERFLY natural history study participants as assessed by Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). Bars to the right of the 0 mark (positive direction) indicate improvement in a specified behavior, while bars to the left of the 0 mark (negative direction) indicate worsening of a specified behavior. BUTTERFLY participants received no doses and were evaluated at month 12. The change in GSV is measured using the OLE study as the baseline.

[0344] FIGS. 66A-66B are graphs illustrating growth scale values (GSV) in receptive communication(FIG.66A) and coping skills (FIG. 66B) of BUTTERFLY study participants over the course of 24 months as measured with Vineland-3. Growth scale values obtained from Vineland-3 were used for modeling disease progression. Modeling accounted for patients with DS who were assessed at baseline and at least one post-baseline visit. Progression for neurotypical peers (dotted lines) was plotted using normative tables from the Vineland-3 manual that show correlations between age equivalents and growth scale values. Progression for BUTTERFLY study participants can be seen from the solid lines. P-values are provided for statistically significant changes.

[0345] FIGS. 67A-67B are plots showing assessment of disease progression as measured by CaregiverGlobal Impression of Change (CaGI-C) (FIG.67A) and Clinical Global Impression of Change (CGI-C) (FIG.67B) in BUTTERFLY study participants over the course of 24 months. For both assessments, change was scored on a 7-point scale with improvement ranging from “very much improved” (scored as 1) to “very much worse” (scored as 7). P-values are provided for statistically significant changes. Y-axes in both figures represent the estimated rating of change. X-axes in both figures represent the timepoints in the study in months. Worsening is denoted by estimated rating of change values above 4, improvementWSGR Ref. No.: 47991-748.601 is denoted by estimated rating of change values below 4, and no change is denoted by estimated rating of change values of 4.

[0346] FIGS. 68A-68B are graphs showing the change in convulsive seizure frequency (FIG. 68A) andGillette FAQ data (FIG.68B) of BUTTERFLY study participants over the course of 24 months. Disease progression modeling accounted for patients with DS who were assessed at baseline and at least one post- baseline visit. The y-axis of FIG.68A represent the estimated percentage of change from baseline in convulsive seizure frequency. The y-axis of FIG.68B represent the estimated total score. X-axes in both graphs represent timepoints of the study in months.

[0347] FIG. 69 is a graphic representation of the dosing frequency of participants in theSWALLOWTAIL / LONGWING open-label extension studies. Dose 1 is administered on Day 1, Dose 2 at Week 16, and Dose 3 at Week 32. Patients who tolerated these treatment doses were dosed every 16 weeks thereafter. Follow-up assessments were done 24 weeks after the last dose.

[0348] FIGS. 70A-70C show comparisons of Vineland-3 data from SWALLOWTAIL / LONGWINGwith the BUTTERFLY DS natural history study. Negative values for the estimated change in GSV indicate worsening in the Vineland-3 subdomain, and positive values for the estimated change in GSVindicate improvements in the Vineland-3 subdomain. FIG. 70A shows a comparison of the change inVineland-3 subdomain GSVs for SWALLOWTAIL / LONGWING (bars with hatch fill) from the OLE baseline. Analysis was based on a mixed-effects model for repeated measures with an unstructured covariance structure. Data from the BUTTERFLY DS natural history study (solid fill bars) through Month 24 was analyzed with machine learning. Baseline covariates in BUTTERFLY including baseline score, convulsive seizure onset age, BMI, age, weight, and baseline seizure frequency matched to SWALLOWTAIL / LONGWING patient population means. SWALLOWTAIL / LONGWING sample size: n=48 at screen, n=28 at Week 48 and n=15 at Week 64, except in Fine Motor where n=45 at screen, n=28 at Week 48, and n=14 at Week 64. BUTTERFLY sample size: n=36 at screen and n=25 at Month 12, except n=24 at Month 12 for Interpersonal Relationships and n=31 at screen and n=18 at Month 12 for Fine Motor. CI, confidence interval; GSV, growth scale value; OLE, open-label extension. FIG.70B shows the comparison for receptive communication, and FIG.70C shows the comparison for interpersonal relationships. In FIGS.70B-70C, triangles represent data from SWALLOWTAIL / LONGWING OLE studies while squares represent data from the BUTTERFLY study.

[0349] FIGS. 71A-71B are data showing improvements in overall clinical status that were observedwithin the first 9 months of treatment in Phase 1 / 2a and continued with ongoing treatment in the OLEs. FIG.71A shows a bar chart of data for Clinical Global Impression of Change (CGI-C)* and FIG.71B shows a bar chart of data for Caregiver Global Impression of Change (CaGI-C)* through 24 months of the SWALLOWTAIL and LONGWING OLE studies. Phase 1 / 2a data-cut: December 12, 2023 (after end of study); OLE data-cut: June 28, 2024. *CGI-C and CaGI-C assessments are scored on a Likert scale with seven response options: 1 (Very much improved), 2 (Much improved), 3 (Minimally improved), 4 (No change), 5 (Minimally worse), 6 (Much worse) or 7 (Very much worse). Data cutoff was DecemberWSGR Ref. No.: 47991-748.601 12, 2023, for MONARCH / ADMIRAL. †Mixed-effects model for repeated measures constructed using data through Month 24 from enrolled patients in OLE studies.

[0350] FIG. 72 is a bar chart showing EuroQol visual analogue scale (EQ-VAS) data representing theQuality of Life (QoL) improvements observed in participants at month 4, month 12, and month 24. The Least-Squares (LS) mean change from OLE baseline is shown on the y-axis, and the timepoints in months are shown on the x-axis. An increase in LS mean change indicates improvement. DETAILED DESCRIPTION

[0351] Certain specific details of this description are set forth in order to provide a thoroughunderstanding of various embodiments. However, one skilled in the art will understand that the present disclosure may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments.

[0352] Unless otherwise defined, all technical and scientific terms used herein have the same meaningas commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods, and materials are described below. Definitions

[0353] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the”include plural referents unless the content clearly dictates otherwise.

[0354] It should be noted that the term “or” is generally employed in its sense including “and / or” unlessthe content clearly dictates otherwise. The terms “and / or” and “any combination thereof” and their grammatical equivalents as used herein, can be used interchangeably. These terms can convey that any combination is specifically contemplated. Solely for illustrative purposes, the following phrases “A, B, and / or C” or “A, B, C, or any combination thereof” can mean “A individually; B individually; C individually; A and B; B and C; A and C; and A, B, and C.” The term “or” can be used conjunctively or disjunctively, unless the context specifically refers to a disjunctive use.

[0355] The term “about” or “approximately” can mean within an acceptable error range for theparticular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, within 5-fold, and more preferably within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated, the term “about” meaning within an acceptable error range for the particular value should be assumed.

[0356] As used in this specification and claim(s), the words “comprising” (and any form of comprising,such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not excludeWSGR Ref. No.: 47991-748.601 additional, unrecited elements or method steps. It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the present disclosure, and vice versa. Furthermore, compositions of the present disclosure can be used to achieve methods of the present disclosure.

[0357] Reference in the specification to “embodiments,” “some embodiments,” “an embodiment,” “oneembodiment,” “certain embodiments,” or “other embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least some embodiments, but not necessarily all embodiments, of the present disclosures. To facilitate an understanding of the present disclosure, a number of terms and phrases are defined below.

[0358] The terms “oligonucleotide sequence,” “nucleic acid sequence,” “polynucleic acid sequence,”“nucleotide sequence,” and “nucleotide acid sequence” are used herein interchangeably in its broadest sense and have the identical meaning herein and refer to preferably DNA or RNA. A nucleic acid sequence is a polymer comprising or consisting of nucleotide monomers, which are covalently linked to each other by phosphodiester-bonds of a sugar / phosphate-backbone. The term “nucleic acid sequence” also encompasses modified nucleic acid sequences, such as base-modified, sugar-modified, or backbone- modified, etc., DNA or RNA.

[0359] The term “fragment” or “fragment of a sequence,” which have the identical meaning herein, is ashorter portion of a full-length sequence of e.g., a nucleic acid molecule like DNA or RNA or a protein. Accordingly, a fragment, typically, consists of a sequence that is identical to the corresponding stretch within the full-length sequence. A preferred fragment of a sequence in the context of the present invention consists of a continuous stretch of entities, such as nucleotides or amino acids corresponding to a continuous stretch of entities in the molecule the fragment is derived from, which represents at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, at least 99.5%, or even 100% of the total (i.e., full-length) molecule from which the fragment is derived. For example, a “fragment” or “functional fragment” of a polynucleotide or a polypeptide is a fragment of the polynucleotide or the polypeptide that is shorter than the full-length, immature, or mature nucleotide or polypeptide and has at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99%, at least 99.5%, or even 100% or more of the activity of the full-length mature reference polynucleotide or polypeptide. Fragments of interest can be made by recombinant, synthetic, or digestive methods.

[0360] The term “recombinant” when used with reference, for example, to a cell, a nucleic acid, aprotein, or a vector, indicates that the cell, nucleic acid, protein, or vector has been modified by or is the result of laboratory methods. Thus, for example, the term “recombinant polynucleotide” can refer to aWSGR Ref. No.: 47991-748.601 polynucleotide that is not naturally occurring and are synthesized or manipulated in vitro, such as polynucleotides produced by laboratory methods. A recombinant polynucleotide can be synthesized in a laboratory and / or can be prepared by using recombinant DNA technology by using enzymatic modification of DNA, such as enzymatic restriction digestion, ligation, and cloning. A recombinant polypeptide can be prepared by in vitro transcription of a recombinant DNA followed by in vitro translation of the produced messenger RNA (mRNA). Alternatively, under suitable conditions, a recombinant polynucleic acid or RNA can be incorporated into a cell and a recombinant polypeptide can be expressed within the cell. Recombinant proteins can include amino acid residues not found within the native (non-recombinant) form of the protein or can include amino acid residues that have been modified, e.g., labeled.

[0361] The term “isolated” means separated from constituents, cellular and otherwise, in which thepolynucleotide, polypeptide, protein, or fragments thereof, are normally associated with in nature. For example, with respect to a polynucleotide, an isolated polynucleotide is one that is separated from the 5’ and 3’ ends with which it is normally associated in the naturally occurring sequence. As is apparent to those of skill in the art, a non-naturally occurring polynucleotide, polypeptide, protein, or fragments thereof, does not require “isolation” to distinguish it from its naturally occurring counterpart. In addition, a “concentrated,” “separated,” or “diluted” polynucleotide, polypeptide, protein, or fragments thereof, is distinguishable from its naturally occurring counterpart in that the concentration or number of molecules per volume is greater than “concentrated,” or less than “separated” or “diluted,” than that of its naturally occurring counterpart.

[0362] As used herein, "nucleotide" means a nucleoside further comprising a phosphate linking group.As used herein, "linked nucleosides" may or may not be linked by phosphate linkages and thus includes, but is not limited to, "linked nucleotides." As used herein, "linked nucleosides" are nucleosides that are connected in a continuous sequence (i.e., no additional nucleosides are present between those that are linked).

[0363] As used herein, "nucleobase" means a group of atoms that can be linked to a sugar moiety tocreate a nucleoside that is capable of incorporation into an oligonucleotide, and wherein the group of atoms is capable of bonding with a complementary naturally occurring nucleobase of another oligonucleotide or nucleic acid. Nucleobases may be naturally occurring or may be modified.

[0364] As used herein, "nucleoside" means a compound comprising a nucleobase moiety and a sugarmoiety. Nucleosides include, but are not limited to, naturally occurring nucleosides (as found in DNA and RNA) and modified nucleosides. Nucleosides may be linked to a phosphate moiety.

[0365] As used herein, "naturally occurring sugar moiety" means a ribofuranosyl as found in naturallyoccurring RNA or a deoxyribofuranosyl as found in naturally occurring DNA.

[0366] As used herein, "sugar moiety" means a naturally occurring sugar moiety or a modified sugarmoiety of a nucleoside.

[0367] As used herein, "modified sugar moiety" means a substituted sugar moiety, a bicyclic or tricyclicsugar moiety, or a sugar surrogate.WSGR Ref. No.: 47991-748.601

[0368] The term “antisense oligonucleotide,” as used herein, refers to synthetic antinucleotideoligonucleotide (ASO) or antisense oligonucleotide analogs usually between 12 and 30 nucleotides in length that are designed to hybridize to RNA by Watson-Crick base pairing. ASOs can be designed to bind to protein coding RNAs (mRNAs) as well as noncoding RNAs such as microRNAs or large noncoding RNAs. After binding to the targeted RNA, the ASO can modulate the function of the targeted RNA by several different mechanisms, including degradation of the pre-mRNA in the nucleus or mature RNA in the cytoplasm by RNase H1, and degradation of RNA in the cytoplasm by the RISC complex (Ago2) or ribozymes or DNAzymes. ASOs can also modulate RNA function by nondegradative mechanisms such as splicing or polyadenylation modulation in the nucleus and modulate protein translation in the cytoplasm.

[0369] The term “to hybridize” means to form hydrogen bond, which may be via Watson-Crick,Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nucleotide bases. “Complementary,” as used herein, refers to the capacity for precise pairing between two nucleotides. The oligonucleotide and the DNA or RNA are complementary to each other when a sufficient number of corresponding positions in each molecule are occupied by nucleotides which can hydrogen bond with each other.

[0370] The terms “identical” or percent “identity,” in the context of two or more nucleic acid orpolypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same (i.e., 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, 99.8%, 99.9%, or 100% identity over a specified region, e.g., of the entire polypeptide sequences of the invention or individual domains of the polypeptides of the invention), when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using a sequence comparison algorithm or by manual alignment and visual inspection. Such sequences that are at least about 80% identical are said to be “substantially identical.” In some embodiments, two sequences are 100% identical. In some embodiments, two sequences are 100% identical over the entire length of one of the sequences (e.g., the shorter of the two sequences where the sequences have different lengths). In various embodiments, identity may refer to the complement of a test sequence.

[0371] In some embodiments, the identity exists over a region that is at least about 2 to about 400 aminoacids or nucleotides in length. In some embodiments, the identity exists over a region that is at least about 2 to about 390, at least about 2 to about 380, at least about 2 to about 370, at least about 2 to about 360, at least about 2 to about 350, at least about 2 to about 340, at least about 2 to about 330, at least about 2 to about 320, at least about 2 to about 310, at least about 2 to about 300, at least about 2 to about 290, at least about 2 to about 280, at least about 2 to about 270, at least about 2 to about 260, at least about 2 to about 250, at least about 2 to about 200, at least about 2 to about 150, at least about 2 to about 100 amino acids or nucleotides in length. In some embodiments, the identity exists over a region that is at least about 2 to about 90, at least about 2 to about 85, at least about 2 to about 80, at least about 2 to about 75, at least about 2 to about 70, at least about 2 to about 65, at least about 2 to about 60, at least about 2 toWSGR Ref. No.: 47991-748.601 about 55, at least about 2 to about 50, at least about 2 to about 45, at least about 2 to about 40, at least about 2 to about 35, at least about 2 to about 30, at least about 2 to about 25, at least about 2 to about 20, at least about 2 to about 10, or at least about 2 to about 5 amino acids or nucleotides in length.

[0372] In some embodiments, the identity exists over a region that is at least about 3 to about 400, about4 to about 400, about 5 to about 400, about 6 to about 400, about 7 to about 400, about 8 to about 400, about 9 to about 400, about 10 to about 400, about 11 to about 400, about 12 to about 400, about 13 to about 400, about 14 to about 400, about 15 to about 400, about 16 to about 400, about 17 to about 400, about 18 to about 400, about 19 to about 400, about 20 to about 400, about 21 to about 400, about 22 to about 400, about 23 to about 400, about 24 to about 400, about 25 to about 400, about 26 to about 400, about 27 to about 400, about 28 to about 400, about 29 to about 400, about 30 to about 400, about 31 to about 400, about 32 to about 400, about 33 to about 400, about 34 to about 400, about 35 to about 400 amino acids or nucleotides in length. In some embodiments, the identity exists over a region that is at least about 40 to about 400, about 45 to about 400, about 50 to about 400, about 55 to about 400, about 60 to about 400, about 61 to about 400, about 62 to about 400, about 63 to about 400, about 64 to about 400, about 65 to about 400, about 66 to about 400, about 67 to about 400, about 68 to about 400, about 69 to about 400, about 70, to about 400, about 71 to about 400, about 72 to about 400, about 73 to about 400, about 74 to about 400, about 75 to about 400, about 80 to about 400, about 85 to about 400, about 90 to about 400, about 100 to about 400, about 150 to about 400, about 200 to about 400, about 250 to about 400, about 300 to about 400, or about 350 to about 400 amino acids or nucleotides in length.

[0373] In some embodiments, the identity exists over a region that is at least about 2 to about 343, about3 to about 343, about 4 to about 343, about 7 to about 343, about 9 to about 343, about 11 to about 343, about 15 to about 343, about 16 to about 343, about 20 to about 343, about 25 to about 343, about 62 to about 343, about 2 to about 317, about 3 to about 317, about 4 to about 317, about 7 to about 317, about 9 to about 317, about 11 to about 317, about 15 to about 317, about 16 to about 317, about 20 to about 317, about 25 to about 317, about 62 to about 317, about 2 to about 300, about 3 to about 300, about 4 to about 300, about 7 to about 300, about 9 to about 300, about 11 to about 300, about 15 to about 300, about 16 to about 300, about 20 to about 300, about 25 to about 300, about 62 to about 300, about 2 to about 62, about 3 to about 62, about 4 to about 62, about 7 to about 62, about 9 to about 62, about 11 to about 62, about 15 to about 62, about 16 to about 62, about 20 to about 62, or about 25 to about 62 amino acids or nucleotides in length.

[0374] The term “genetically modified” means containing and / or expressing a foreign gene or nucleicacid sequence which in turn, modifies the genotype or phenotype of the cell or its progeny. In other words, it refers to any addition, deletion, or disruption to a cell’s endogenous nucleotides.

[0375] The term “operably linked” can refer to a functional relationship between two or more nucleicacid sequences, e.g., a functional relationship of a transcriptional regulatory or signal sequence to a transcribed sequence. For example, a target motif or a nucleic acid encoding a target motif is operably linked to a coding sequence if it is expressed as a preprotein that participates in targeting the polypeptide encoded by the coding sequence to a cell membrane, intracellular, or an extracellular compartment. ForWSGR Ref. No.: 47991-748.601 example, a signal peptide or a nucleic acid encoding a signal peptide is operably linked to a coding sequence if it is expressed as a preprotein that participates in the secretion of the polypeptide encoded by the coding sequence. For example, a promoter is operably linked if it stimulates or modulates the transcription of the coding sequence.

[0376] The term “subject” or “patient” encompasses vertebrates or mammals. Examples of mammalsinclude, but are not limited to, any member of the mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice, and guinea pigs, and the like. In one aspect, the mammal is a human. The term “animal” as used herein comprises human beings and non-human animals. In one embodiment, a “non-human animal” is a mammal, for example, a rodent such as rat or a mouse. In one embodiment, a non-human animal is a mouse.

[0377] A “control” is an alternative subject or sample used in an experiment for comparison purpose. Acontrol can be “positive” or “negative.” Methods of Treatment

[0378] In some aspects, provided herein is a method of treating or preventing a disease or conditioncharacterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof comprising administering to the human subject a pharmaceutical composition comprising a compound at a first dose of about 0.1, 0.5, 1, 2.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200 mg, wherein the compound is an antisense oligomer (ASO) that comprises a sequence with at least 80% sequence identity to any one of SEQ ID NOs: 21-67, 210-256 or 304-1099, thereby treating or preventing the disease or condition in the human subject. In some embodiments, the ASO comprises a sequence with at least 80% sequence identity to any one of the sequences listed in Tables 4A, 4B, 5A, 5B, 6, 7A, and 7B, thereby treating or preventing the disease or condition in the human subject.

[0379] In some aspects, provided herein is a method of treating or preventing a disease or conditioncharacterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof comprising administering to the human subject a pharmaceutical composition comprising a first dose of a compound, wherein the compound is an ASO that comprises a sequence with at least 80% sequence identity to any one of SEQ ID NOs: 21-67, 210-256 or 304-1099, thereby treating or preventing the disease or condition in the human subject; wherein the human subject is at most 18 years old. In some embodiments, the ASO comprises a sequence with at least 80% sequence identity to any one of the sequences listed in listed in Tables 4A, 4B, 5A, 5B, 6, 7A, and 7B, thereby treating or preventing the disease or condition in the human subject; wherein the human subject is at most 18 years old.

[0380] In some aspects, provided herein is a method of treating or preventing a disease or conditioncharacterized by a reduced expression or function of NaV1.1 protein in a human subject in need thereof comprising administering to the human subject a pharmaceutical composition comprising a single dose ofWSGR Ref. No.: 47991-748.601 an antisense oligomer (ASO), wherein the ASO comprises a sequence with at least 80% sequence identity to any one of SEQ ID NOs: 21-67, 210-256 or 304-1099, thereby treating or preventing the disease or condition in the human subject. In some embodiments, the ASO comprises a sequence with at least 80% sequence identity to any one of any one of the sequences listed in listed in Tables 4A, 4B, 5A, 5B, 6, 7A, and 7B, thereby treating or preventing the disease or condition in the human subject.

[0381] In some embodiments, the pharmaceutical composition is administered into the intrathecal spaceof the human subject. In some embodiments, the pharmaceutical composition is administered into the cerebrospinal fluid of the human subject. In some embodiments, the pharmaceutical composition is administered into the brain of the human subject. In some embodiments, the pharmaceutical composition is administered into the cerebrospinal fluid in the brain of the human subject.

[0382] In some embodiments, the pharmaceutical composition is administered as a bolus injection. Insome embodiments, the pharmaceutical composition is administered by infusion with a delivery pump. In some embodiments, the pharmaceutical composition is administered by intracerebroventricular injection. In some embodiments, the pharmaceutical composition is administered by intrathecal injection. Therapeutic Dose

[0383] In some embodiments, the first dose is a single dose. In some embodiments, the method furthercomprises assessing tolerability or effectiveness of the pharmaceutical composition.

[0384] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising a compound as described herein at a first dose of about 0.1, 0.5, 1, 2.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200 mg.

[0385] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from about 0.1 to about 1000 mg, from about 0.2 to about 1000 mg, from about 0.3 to about 1000 mg, from about 0.4 to about 1000 mg, from about 0.5 to about 1000 mg, from about 0.6 to about 1000 mg, from about 0.7 to about 1000 mg, from about 0.8 to about 1000 mg, from about 0.9 to about 1000 mg, 1 to about 1000 mg, from about 2 to about 1000 mg, from about 3 to about 1000 mg, from about 4 to about 1000 mg, from about 5 to about 1000 mg, from about 6 to about 1000 mg, from about 7 to about 1000 mg, from about 8 to about 1000 mg, from about 9 to about 1000 mg, from about 10 to about 1000 mg, from about 15 to about 1000 mg, from about 20 to about 1000 mg, from about 25 to about 1000 mg, from about 30 to about 1000 mg, from about 35 to about 1000 mg, from about 40 to about 1000 mg, from about 45 to about 1000 mg, from about 50 to about 1000 mg, from about 55 to about 1000 mg, from about 60 to about 1000 mg, from about 65 to about 1000 mg, from about 70 to about 1000 mg, from about 75 to about 1000 mg, from about 80 to about 1000 mg, from about 85 to about 1000 mg, from about 90 to about 1000 mg, from about 95 to about 1000 mg, from about 100 to about 1000 mg, from about 150 to about 1000 mg, from about 200 to about 1000 mg, from about 250 to about 1000 mg, from about 300 to about 1000 mg, from about 350 to about 1000 mg, from about 400 to about 1000 mg, fromWSGR Ref. No.: 47991-748.601 about 450 to about 1000 mg, from about 500 to about 1000 mg, from about 550 to about 1000 mg, from about 600 to about 1000 mg, from about 650 to about 1000 mg, from about 700 to about 1000 mg, from about 750 to about 1000 mg, from about 800 to about 1000 mg, from about 850 to about 1000 mg, from about 900 to about 1000 mg, or from about 950 to about 1000 mg.

[0386] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from 0.1 to 1000 mg, from 0.2 to 1000 mg, from 0.3 to 1000 mg, from 0.4 to 1000 mg, from 0.5 to 1000 mg, from 0.6 to 1000 mg, from 0.7 to 1000 mg, from 0.8 to 1000 mg, from 0.9 to 1000 mg, 1 to 1000 mg, from 2 to 1000 mg, from 3 to 1000 mg, from 4 to 1000 mg, from 5 to 1000 mg, from 6 to 1000 mg, from 7 to 1000 mg, from 8 to 1000 mg, from 9 to 1000 mg, from 10 to 1000 mg, from 15 to 1000 mg, from 20 to 1000 mg, from 25 to 1000 mg, from 30 to 1000 mg, from 35 to 1000 mg, from 40 to 1000 mg, from 45 to 1000 mg, from 50 to 1000 mg, from 55 to 1000 mg, from 60 to 1000 mg, from 65 to 1000 mg, from 70 to 1000 mg, from 75 to 1000 mg, from 80 to 1000 mg, from 85 to 1000 mg, from 90 to 1000 mg, from 95 to 1000 mg, from 100 to 1000 mg, from 150 to 1000 mg, from 200 to 1000 mg, from 250 to 1000 mg, from 300 to 1000 mg, from 350 to 1000 mg, from 400 to 1000 mg, from 450 to 1000 mg, from 500 to 1000 mg, from 550 to 1000 mg, from 600 to 1000 mg, from 650 to 1000 mg, from 700 to 1000 mg, from 750 to 1000 mg, from 800 to 1000 mg, from 850 to 1000 mg, from 900 to 1000 mg, or from 950 to 1000 mg.

[0387] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from about 0.1 to about 950 mg, from about 0.1 to about 900 mg, from about 0.1 to about 850 mg, from about 0.1 to about 800 mg, from about 0.1 to about 750 mg, from about 0.1 to about 700 mg, from about 0.1 to about 650 mg, from about 0.1 to about 600 mg, from about 0.1 to about 550 mg, from about 0.1 to about 500 mg, from about 0.1 to about 450 mg, from about 0.1 to about 400 mg, from about 0.1 to about 350 mg, from about 0.1 to about 300 mg, from about 0.1 to about 250 mg, from about 0.1 to about 200 mg, from about 0.1 to about 150 mg, from about 0.1 to about 100 mg, from about 0.1 to about 95 mg, from about 0.1 to about 90 mg, from about 0.1 to about 85 mg, from about 0.1 to about 80 mg, from about 0.1 to about 75 mg, from about 0.1 to about 70 mg, from about 0.1 to about 65 mg, from about 0.1 to about 60 mg, from about 0.1 to about 55 mg, from about 0.1 to about 50 mg, from about 0.1 to about 45 mg, from about 0.1 to about 40 mg, from about 0.1 to about 35 mg, from about 0.1 to about 30 mg, from about 0.1 to about mg, from about 0.1 to about 25 mg, from about 0.1 to about 20 mg, from about 0.1 to about 10 mg, from about 0.1 to about 9 mg, from about 0.1 to about 8 mg, from about 0.1 to about 7 mg, from about 0.1 to about 6 mg, from about 0.1 to about 5 mg, from about 0.1 to about 4 mg, from about 0.1 to about 3, from about 0.1 to about 2 mg, from about 0.1 to about 1 mg, from about 0.1 to about 0.9 mg, from about 0.1 to about 0.8 mg, from about 0.1 to about 0.7 mg, from about 0.1 to about 0.6 mg, from about 0.1 to about 0.5 mg, from about 0.1 to about 0.4 mg, from about 0.1 to about 0.3, or from about 0.1 to about 0.2 mg.WSGR Ref. No.: 47991-748.601

[0388] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from 0.1 to 950 mg, from 0.1 to 900 mg, from 0.1 to 850 mg, from 0.1 to 800 mg, from 0.1 to 750 mg, from 0.1 to 700 mg, from 0.1 to 650 mg, from 0.1 to 600 mg, from 0.1 to 550 mg, from 0.1 to 500 mg, from 0.1 to 450 mg, from 0.1 to 400 mg, from 0.1 to 350 mg, from 0.1 to 300 mg, from 0.1 to 250 mg, from 0.1 to 200 mg, from 0.1 to 150 mg, from 0.1 to 100 mg, from 0.1 to 95 mg, from 0.1 to 90 mg, from 0.1 to 85 mg, from 0.1 to 80 mg, from 0.1 to 75 mg, from 0.1 to 70 mg, from 0.1 to 65 mg, from 0.1 to 60 mg, from 0.1 to 55 mg, from 0.1 to 50 mg, from 0.1 to 45 mg, from 0.1 to 40 mg, from 0.1 to 35 mg, from 0.1 to 30 mg, from 0.1 to mg, from 0.1 to 25 mg, from 0.1 to 20 mg, from 0.1 to 10 mg, from 0.1 to 9 mg, from 0.1 to 8 mg, from 0.1 to 7 mg, from 0.1 to 6 mg, from 0.1 to 5 mg, from 0.1 to 4 mg, from 0.1 to 3, from 0.1 to 2 mg, from 0.1 to 1 mg, from 0.1 to 0.9 mg, from 0.1 to 0.8 mg, from 0.1 to 0.7 mg, from 0.1 to 0.6 mg, from 0.1 to 0.5 mg, from 0.1 to 0.4 mg, from 0.1 to 0.3, or from 0.1 to 0.2 mg.

[0389] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from about 1 to about 400 mg, from about 2 to about 400 mg, from about 3 to about 400 mg, from about 4 to about 400 mg, from about 5 to about 400 mg, from about 6 to about 400 mg, from about 7 to about 400 mg, from about 8 to about 400 mg, from about 9 to about 400 mg, from about 10 to about 400 mg, from about 20 to about 400 mg, from about 30 to about 400 mg, from about 40 to about 400 mg, from about 50 to about 400 mg, from about 60 to about 400 mg, from about 70 to about 400 mg, from about 80 to about 400 mg, from about 90 to about 400 mg, from about 100 to about 400 mg, from about 110 to about 400 mg, from about 120 to about 400 mg, from about 130 to about 400 mg, from about140 to about 400 mg, from about 150 to about 400 mg, from about160 to about 400 mg, from about 170 to about 400 mg, from about 180 to about 400 mg, from about 190 to about 400 mg, from about 200 to about 400 mg, from about 210 to about 400 mg, from about 220 to about 400 mg, from about 230 to about 400 mg, from about 240 to about 400 mg, from about 250 to about 400 mg, from about 260 to about 400 mg, from about 270 to about 400 mg, from about 280 to about 400 mg, from about 290 to about 400 mg, from about 300 to about 400 mg, from about 310 to about 400 mg, from about 320 to about 400 mg, from about 330 to about 400 mg, from about 340 to about 400 mg, from about 350 to about 400 mg, from about 360 to about 400 mg, from about 370 to about 400 mg, from about 380 to about 400 mg, or from about 390 to about 400 mg.

[0390] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from 1 to 400 mg, from 2 to 400 mg, from 3 to 400 mg, from 4 to 400 mg, from 5 to 400 mg, from 6 to 400 mg, from 7 to 400 mg, from 8 to 400 mg, from 9 to 400 mg, from 10 to 400 mg, from 20 to 400 mg, from 30 to 400 mg, from 40 to 400 mg, from 50 to 400 mg, from 60 to 400 mg, from 70 to 400 mg, from 80 to 400 mg, from 90 to 400 mg, from 100 to 400 mg, from 110 to 400 mg, from 120 to 400 mg, from 130 to 400 mg, from about 140 to 400 mg, from 150 to 400 mg, from about160 to 400 mg, from 170 to 400 mg, from 180 to 400 mg, from 190 to 400 mg, from 200 to 400 mg, from 210 to 400 mg, from 220 toWSGR Ref. No.: 47991-748.601 400 mg, from 230 to 400 mg, from 240 to 400 mg, from 250 to 400 mg, from 260 to 400 mg, from 270 to 400 mg, from 280 to 400 mg, from 290 to 400 mg, from 300 to 400 mg, from 310 to 400 mg, from 320 to 400 mg, from 330 to 400 mg, from 340 to 400 mg, from 350 to 400 mg, from 360 to 400 mg, from 370 to 400 mg, from 380 to 400 mg, or from 390 to 400 mg.

[0391] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from about 10 to about 390 mg, from about 10 to about 380 mg, from about 10 to about 370 mg, from about 10 to about 360 mg, from about 10 to about 350 mg, from about 10 to about 340 mg, from about 10 to about 330 mg, from about 10 to about 320 mg, from about 10 to about 310 mg, from about 10 to about 300 mg, from about 10 to about 290 mg, from about 10 to about 280 mg, from about 10 to about 270 mg, from about 10 to about 260 mg, from about 10 to about 250 mg, from about 10 to about 240 mg, from about 10 to about 230 mg, from about 10 to about 220 mg, from about 10 to about 210 mg, from about 10 to about 200 mg, from about 10 to about 190 mg, from about 10 to about 180 mg, from about 10 to about 170 mg, from about 10 to about 160 mg, from about 10 to about 150 mg, from about 10 to about 140 mg, from about 10 to about 130 mg, from about 10 to about 120 mg, from about 10 to about 110 mg, from about 10 to about 90 mg, from about 10 to about 80 mg, from about 10 to about 70 mg, from about 10 to about 60 mg, from about 10 to about 50 mg, from about 10 to about 40 mg, from about 10 to about 30 mg, or from about 10 to about 20 mg.

[0392] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of from 10 to 390 mg, from 10 to 380 mg, from 10 to 370 mg, from 10 to 360 mg, from 10 to 350 mg, from 10 to 340 mg, from 10 to 330 mg, from 10 to 320 mg, from 10 to 310 mg, from 10 to 300 mg, from 10 to 290 mg, from 10 to 280 mg, from 10 to 270 mg, from 10 to 260 mg, from 10 to 250 mg, from 10 to 240 mg, from 10 to 230 mg, from 10 to 220 mg, from 10 to 210 mg, from 10 to 200 mg, from 10 to 190 mg, from 10 to 180 mg, from 10 to 170 mg, from 10 to 160 mg, from 10 to 150 mg, from 10 to 140 mg, from 10 to 130 mg, from 10 to 120 mg, from 10 to 110 mg, from 10 to 90 mg, from 10 to 80 mg, from 10 to 70 mg, from 10 to 60 mg, from 10 to 50 mg, from 10 to 40 mg, from 10 to 30 mg, or from 10 to 20 mg.

[0393] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about 30 mg, about 31 mg, about 32 mg, about 33 mg, about 34 mg, about 35 mg, about 36 mg, about 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 61 mg, about 62 mg, about 63 mg, about 64 mg, about 65 mg, about 66 mg, about 67 mg, about 68 mg, about 69WSGR Ref. No.: 47991-748.601 mg, about 70 mg, about 71 mg, about 72 mg, about 73 mg, about 74 mg, about 75 mg, about 76 mg, about 77 mg, about 78 mg, about 79 mg, about 80 mg, about 81 mg, about 82 mg, about 83 mg, about 84 mg, about 85 mg, about 86 mg, about 87 mg, about 88 mg, about 89 mg, about 90 mg, about 91 mg, about 92 mg, about 93 mg, about 94 mg, about 95 mg, about 96 mg, about 97 mg, about 98 mg, about 99 mg, about 100 mg, about 101 mg, about 102 mg, about 103 mg, about 104 mg, about 105 mg, about 106 mg, about 107 mg, about 108 mg, about 109 mg, about 110 mg, about 111 mg, about 112 mg, about 113 mg, about 114 mg, about 115 mg, about 116 mg, about 117 mg, about 118 mg, about 119 mg, about 120 mg, about 121 mg, about 122 mg, about 123 mg, about 124 mg, about 125 mg, about 126 mg, about 127 mg, about 128 mg, about 129 mg, about 130 mg, about 131 mg, about 132 mg, about 133 mg, about 134 mg, about 135 mg, about 136 mg, about 137 mg, about 138 mg, about 139 mg, about 140 mg, about 141 mg, about 142 mg, about 143 mg, about 144 mg, about 145 mg, about 146 mg, about 147 mg, about 148 mg, about 149 mg, about 150 mg, about 151 mg, about 152 mg, about 153 mg, about 154 mg, about 155 mg, about 156 mg, about 157 mg, about 158 mg, about 159 mg, about 160 mg, about 161 mg, about 162 mg, about 163 mg, about 164 mg, about 165 mg, about 166 mg, about 167 mg, about 168 mg, about 169 mg, about 170 mg, about 171 mg, about 172 mg, about 173 mg, about 174 mg, about 175 mg, about 176 mg, about 177 mg, about 178 mg, about 179 mg, about 180 mg, about 181 mg, about 182 mg, about 183 mg, about 184 mg, about 185 mg, about 186 mg, about 187 mg, about 188 mg, about 189 mg, about 190 mg, about 191 mg, about 192 mg, about 193 mg, about 194 mg, about 195 mg, about 196 mg, about 197 mg, about 198 mg, about 199 mg, about 200 mg, about 201 mg, about 202 mg, about 203 mg, about 204 mg, about 205 mg, about 206 mg, about 207 mg, about 208 mg, about 209 mg, about 210 mg, about 211 mg, about 212 mg, about 213 mg, about 214 mg, about 215 mg, about 216 mg, about 217 mg, about 218 mg, about 219 mg, about 220 mg, about 221 mg, about 222 mg, about 223 mg, about 224 mg, about 225 mg, about 226 mg, about 227 mg, about 228 mg, about 229 mg, about 230 mg, about 231 mg, about 232 mg, about 233 mg, about 234 mg, about 235 mg, about 236 mg, about 237 mg, about 238 mg, about 239 mg, about 240 mg, about 241 mg, about 242 mg, about 243 mg, about 244 mg, about 245 mg, about 246 mg, about 247 mg, about 248 mg, about 249 mg, about 250 mg, about 251 mg, about 252 mg, about 253 mg, about 254 mg, about 255 mg, about 256 mg, about 257 mg, about 258 mg, about 259 mg, about 260 mg, about 261 mg, about 262 mg, about 263 mg, about 264 mg, about 265 mg, about 266 mg, about 267 mg, about 268 mg, about 269 mg, about 270 mg, about 271 mg, about 272 mg, about 273 mg, about 274 mg, about 275 mg, about 276 mg, about 277 mg, about 278 mg, about 279 mg, about 280 mg, about 281 mg, about 282 mg, about 283 mg, about 284 mg, about 285 mg, about 286 mg, about 287 mg, about 288 mg, about 289 mg, about 290 mg, about 291 mg, about 292 mg, about 293 mg, about 294 mg, about 295 mg, about 296 mg, about 297 mg, about 298 mg, about 299 mg, about 300 mg, about 301 mg, about 302 mg, about 303 mg, about 304 mg, about 305 mg, about 306 mg, about 307 mg, about 308 mg, about 309 mg, about 310 mg, about 311 mg, about 312 mg, about 313 mg, about 314 mg, about 315 mg, about 316 mg, about 317 mg, about 318 mg, about 319 mg, about 320 mg, about 321 mg, about 322 mg, about 323 mg, about 324 mg, about 325 mg, about 326 mg, about 327 mg, about 328 mg, about 329 mg, about 330 mg, about 331 mg, about 332 mg, about 333 mg, about 334 mg, about 335 mg, about 336 mg, about 337WSGR Ref. No.: 47991-748.601 mg, about 338 mg, about 339 mg, about 340 mg, about 341 mg, about 342 mg, about 343 mg, about 344 mg, about 345 mg, about 346 mg, about 347 mg, about 348 mg, about 349 mg, about 350 mg, about 351 mg, about 352 mg, about 353 mg, about 354 mg, about 355 mg, about 356 mg, about 357 mg, about 358 mg, about 359 mg, about 360 mg, about 361 mg, about 362 mg, about 363 mg, about 364 mg, about 365 mg, about 366 mg, about 367 mg, about 368 mg, about 369 mg, about 370 mg, about 371 mg, about 372 mg, about 373 mg, about 374 mg, about 375 mg, about 376 mg, about 377 mg, about 378 mg, about 379 mg, about 380 mg, about 381 mg, about 382 mg, about 383 mg, about 384 mg, about 385 mg, about 386 mg, about 387 mg, about 388 mg, about 389 mg, about 390 mg, about 391 mg, about 392 mg, about 393 mg, about 394 mg, about 395 mg, about 396 mg, about 397 mg, about 398 mg, about 399 mg, or about 400 mg.

[0394] In some embodiments, the method as described herein comprises administering to the humansubject a pharmaceutical composition comprising the compound as described herein at a first dose of 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, 54 mg, 55 mg, 56 mg, 57 mg, 58 mg, 59 mg, 60 mg, 61 mg, 62 mg, 63 mg, 64 mg, 65 mg, 66 mg, 67 mg, 68 mg, 69 mg, 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, 76 mg, 77 mg, 78 mg, 79 mg, 80 mg, 81 mg, 82 mg, 83 mg, 84 mg, 85 mg, 86 mg, 87 mg, 88 mg, 89 mg, 90 mg, 91 mg, 92 mg, 93 mg, 94 mg, 95 mg, 96 mg, 97 mg, 98 mg, 99 mg, 100 mg, 101 mg, 102 mg, 103 mg, 104 mg, 105 mg, 106 mg, 107 mg, 108 mg, 109 mg, 110 mg, 111 mg, 112 mg, 113 mg, 114 mg, 115 mg, 116 mg, 117 mg, 118 mg, 119 mg, 120 mg, 121 mg, 122 mg, 123 mg, 124 mg, 125 mg, 126 mg, 127 mg, 128 mg, 129 mg, 130 mg, 131 mg, 132 mg, 133 mg, 134 mg, 135 mg, 136 mg, 137 mg, 138 mg, 139 mg, 140 mg, 141 mg, 142 mg, 143 mg, 144 mg, 145 mg, 146 mg, 147 mg, 148 mg, 149 mg, 150 mg, 151 mg, 152 mg, 153 mg, 154 mg, 155 mg, 156 mg, 157 mg, 158 mg, 159 mg, 160 mg, 161 mg, 162 mg, 163 mg, 164 mg, 165 mg, 166 mg, 167 mg, 168 mg, 169 mg, 170 mg, 171 mg, 172 mg, 173 mg, 174 mg, 175 mg, 176 mg, 177 mg, 178 mg, 179 mg, 180 mg, 181 mg, 182 mg, 183 mg, 184 mg, 185 mg, 186 mg, 187 mg, 188 mg, 189 mg, 190 mg, 191 mg, 192 mg, 193 mg, 194 mg, 195 mg, 196 mg, 197 mg, 198 mg, 199 mg, 200 mg, 201 mg, 202 mg, 203 mg, 204 mg, 205 mg, 206 mg, 207 mg, 208 mg, 209 mg, 210 mg, 211 mg, 212 mg, 213 mg, 214 mg, 215 mg, 216 mg, 217 mg, 218 mg, 219 mg, 220 mg, 221 mg, 222 mg, 223 mg, 224 mg, 225 mg, 226 mg, 227 mg, 228 mg, 229 mg, 230 mg, 231 mg, 232 mg, 233 mg, 234 mg, 235 mg, 236 mg, 237 mg, 238 mg, 239 mg, 240 mg, 241 mg, 242 mg, 243 mg, 244 mg, 245 mg, 246 mg, 247 mg, 248 mg, 249 mg, 250 mg, 251 mg, 252 mg, 253 mg, 254 mg, 255 mg, 256 mg, 257 mg, 258 mg, 259 mg, 260 mg, 261 mg, 262 mg, 263 mg, 264 mg, 265 mg, 266 mg, 267 mg, 268 mg, 269 mg, 270 mg, 271 mg, 272 mg, 273 mg, 274 mg, 275 mg, 276 mg, 277 mg, 278 mg, 279 mg, 280 mg, 281 mg, 282 mg, 283 mg, 284 mg, 285 mg, 286 mg, 287 mg, 288 mg, 289 mg, 290 mg, 291 mg, 292 mg, 293 mg, 294 mg, 295 mg, 296 mg, 297 mg, 298 mg, 299 mg, 300 mg, 301 mg, 302 mg, 303 mg, 304 mg, 305 mg, 306 mg, 307 mg, 308 mg, 309 mg, 310 mg, 311 mg, 312 mg, 313 mg, 314 mg, 315 mg, 316 mg, 317 mg, 318 mg, 319 mg, 320 mg, 321 mg, 322 mg, 323 mg, 324 mg, 325 mg, 326 mg, 327 mg,WSGR Ref. No.: 47991-748.601 328 mg, 329 mg, 330 mg, 331 mg, 332 mg, 333 mg, 334 mg, 335 mg, 336 mg, 337 mg, 338 mg, 339 mg, 340 mg, 341 mg, 342 mg, 343 mg, 344 mg, 345 mg, 346 mg, 347 mg, 348 mg, 349 mg, 350 mg, 351 mg, 352 mg, 353 mg, 354 mg, 355 mg, 356 mg, 357 mg, 358 mg, 359 mg, 360 mg, 361 mg, 362 mg, 363 mg, 364 mg, 365 mg, 366 mg, 367 mg, 368 mg, 369 mg, 370 mg, 371 mg, 372 mg, 373 mg, 374 mg, 375 mg, 376 mg, 377 mg, 378 mg, 379 mg, 380 mg, 381 mg, 382 mg, 383 mg, 384 mg, 385 mg, 386 mg, 387 mg, 388 mg, 389 mg, 390 mg, 391 mg, 392 mg, 393 mg, 394 mg, 395 mg, 396 mg, 397 mg, 398 mg, 399 mg, or 400 mg. Dosing Regimen

[0395] The terms “schedule,” “schedules,” “time interval,” and “time intervals” are used hereininterchangeably in their broadest sense. In some embodiments, the method or dosing regimen as described herein comprises administering to the human subject multiple doses of a pharmaceutical composition comprising an amount of a compound as described herein. In some embodiments, the multiple doses comprise loading doses and maintenance doses that are administered at defined schedules or time intervals. In some embodiments, the multiple doses comprise at least one loading dose and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses comprise at least two loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses comprise two loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses comprise at least three loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses comprise two loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses comprise three loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses comprise two loading doses and at least two maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses comprise three loading doses and at least two maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses comprise two loading doses and at least three maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses comprise three loading doses and at least three maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses comprise two loading doses and at least four maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses comprise three loading doses and at least four maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses comprise a first loading dose, a second loading dose, and two or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses comprise a first loading dose, a second loading dose, and three or more maintenance doses following the second loading dose that are each administered at defined time intervals. In someWSGR Ref. No.: 47991-748.601 embodiments, the multiple doses comprise a first loading dose, a second loading dose, and four or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and two or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and three or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and four or more maintenance doses following the second loading dose that are each administered at defined time intervals.

[0396] In some embodiments, the multiple doses consist of loading doses and maintenance doses thatare administered at defined time intervals. In some embodiments, the multiple doses consist of at least one loading dose and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses consist of at least two loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses consist of two loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses consist of at least three loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses consist of two loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses consist of three loading doses and at least one maintenance dose that are administered at defined time intervals. In some embodiments, the multiple doses consist of two loading doses and at least two maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses consist of three loading doses and at least two maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses consist of two loading doses and at least three maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses consist of three loading doses and at least three maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses consist of two loading doses and at least four maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses consist of three loading doses and at least four maintenance doses that are administered at defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, and two or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, and three or more maintenance doses following the second loading dose that are each administered atWSGR Ref. No.: 47991-748.601 defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, and four or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, a third loading dose, and two or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, a third loading dose, and three or more maintenance doses following the second loading dose that are each administered at defined time intervals. In some embodiments, the multiple doses consist of a first loading dose, a second loading dose, a third loading dose, and four or more maintenance doses following the second loading dose that are each administered at defined time intervals.

[0397] In some embodiments, the one or more maintenance doses comprises at least one maintenancedose. In some embodiments, the one or more maintenance doses comprises at least two maintenance doses. In some embodiments, the one or more maintenance doses comprises at least three maintenance doses. In some embodiments, the one or more maintenance doses comprises at least four maintenance doses. In some embodiments, the one or more maintenance doses comprises at least five maintenance doses. In some embodiments, the one or more maintenance doses comprises at least six maintenance doses. In some embodiments, the one or more maintenance doses comprises at least seven maintenance doses. In some embodiments, the one or more maintenance doses comprises at least eight maintenance doses. In some embodiments, the one or more maintenance doses comprises at least nine maintenance doses. In some embodiments, the one or more maintenance doses comprises at least ten maintenance doses. In some embodiments, the one or more maintenance doses comprises at least eleven maintenance doses. In some embodiments, the one or more maintenance doses comprises at least twelve maintenance doses. In some embodiments, the one or more maintenance doses comprise more than two maintenance doses. In some embodiments, the one or more maintenance doses comprise more than three maintenance doses. In some embodiments, the one or more maintenance doses comprise more than four maintenance doses. In some embodiments, the one or more maintenance doses consists of at least one maintenance dose. In some embodiments, the one or more maintenance doses consists of at least two maintenance doses. In some embodiments, the one or more maintenance doses consists of at least three maintenance doses. In some embodiments, the one or more maintenance doses consists of at least four maintenance doses. In some embodiments, the one or more maintenance doses consists of at least five maintenance doses. In some embodiments, the one or more maintenance doses consists of at least six maintenance doses. In some embodiments, the one or more maintenance doses consists of at least seven maintenance doses. In some embodiments, the one or more maintenance doses consists of at least eight maintenance doses. In some embodiments, the one or more maintenance doses consists of at least nine maintenance doses. In some embodiments, the one or more maintenance doses consists of at least ten maintenance doses. In some embodiments, the one or more maintenance doses consists of at least eleven maintenanceWSGR Ref. No.: 47991-748.601 doses. In some embodiments, the one or more maintenance doses consists of at least twelve maintenance doses.

[0398] In some embodiments, the subject continues receiving standard of care, prior to, during, and / orafter administration of a pharmaceutical composition comprising an amount of a compound as described herein, for instance, receiving administration of an antiepileptic drug (AED), e.g., clobazam, fenfluramine, stiripentol, valproic acid, cannabidiol, or levetiracetam. In some cases, the AED administered to the subject is not an AED primarily acting as a sodium channel blocker (e.g., phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide).

[0399] Dosing Regimen: Amounts of Compound in Loading and Maintenance Doses

[0400] In some embodiments, the method or dosing regimen as described herein comprisesadministering to the human subject multiple doses of a pharmaceutical composition comprising an amount of a compound as described herein. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 20 mg, 25 mg, 30 mg, 35 mg 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, or 100 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 20 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 25 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 80 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 85 mg. InWSGR Ref. No.: 47991-748.601 some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 90 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 95 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the one or more maintenance doses is about 100 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 20 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 25 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 80 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 85 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 90 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 95 mg. In someWSGR Ref. No.: 47991-748.601 embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses is about 100 mg.

[0401] In some embodiments, the amount of the compound in each dose of the first loading dose and thesecond loading dose is about 20 mg, and the amount of the compound in each of the one or more maintenance doses is about 15 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 25 mg, and the amount of the compound in each of the one or more maintenance doses is about 20 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 30 mg, and the amount of the compound in each of the one or more maintenance doses is about 20 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 30 mg, and the amount of the compound in each of the one or more maintenance doses is about 25 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 35 mg, and the amount of the compound in each of the one or more maintenance doses is about 25 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 35 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 40 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 40 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 45 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 45 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 45 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 55 mg, and the amount of the compound in each of the one or more maintenance doses isWSGR Ref. No.: 47991-748.601 about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 55 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or moreWSGR Ref. No.: 47991-748.601 maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound inWSGR Ref. No.: 47991-748.601 each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 85 mg, and theWSGR Ref. No.: 47991-748.601 amount of the compound in each of the one or more maintenance doses is about 80 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 80 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 85 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loadingWSGR Ref. No.: 47991-748.601 dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 80 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 85 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 90 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the firstWSGR Ref. No.: 47991-748.601 loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 80 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 85 mg. In some embodiments, the amount of the compound in each dose of the first loading dose and the second loading dose is about 100 mg, and the amount of the compound in each of the one or more maintenance doses is about 90 mg.

[0402] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the third loading dose is about 20 mg, and the amount of the compound in each of the one or more maintenance doses is about 15 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 25 mg, and the amount of the compound in each of the one or more maintenance doses is about 20 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 30 mg, and the amount of the compound in each of the one or more maintenance doses is about 20 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 30 mg, and the amount of the compound in each of the one or more maintenance doses is about 25 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 35 mg, and the amount of the compound in each of the one or more maintenance doses is about 25 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 35 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 40 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 40 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 45 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 45 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 45 mg, and the amount of the compound in each of the one orWSGR Ref. No.: 47991-748.601 more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 55 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 55 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In someWSGR Ref. No.: 47991-748.601 embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 65 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in eachWSGR Ref. No.: 47991-748.601 dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 75 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 80 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loadingWSGR Ref. No.: 47991-748.601 dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 85 mg, and the amount of the compound in each of the one or more maintenance doses is about 80 mg.

[0403] In some embodiments, the amount of the compound in each dose of the first loading dose, thesecond loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 35 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 40 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loadingWSGR Ref. No.: 47991-748.601 dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 50 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 55 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 60 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 65 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 70 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 75 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 80 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 90 mg, and the amount of the compound in each of the one or more maintenance doses is about 85 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, and the third loading dose is about 95 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg. In some embodiments, the amount of the compound in each dose of the first loading dose, the second loading dose, ...

Claims

WSGR Ref. No.: 47991-748.601 CLAIMS WHAT IS CLAIMED IS:

1. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and a first maintenance dose following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the first maintenance dose independently contains the compound at an amount of from about 25 mg to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, and the first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the second loading dose.

2. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:WSGR Ref. No.: 47991-748.601(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and a first maintenance dose following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the first maintenance dose independently contains the compound at an amount of from about 25 mg to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, the third loading dose is administered from 2 weeks to 12 weeks after the second loading dose, and the first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the third loading dose.WSGR Ref. No.: 47991-748.6013. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; and administering to the human subject a first maintenance dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 169th day of treatment, (b) 4 months after the second loading dose, or (c) 16 weeks after the second loading dose.WSGR Ref. No.: 47991-748.6014. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; administering to the human subject a third loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 85th day of treatment, (b) 1 month after the second loading dose, or (c) 4 weeks after the second loading dose; and administering to the human subject a first maintenance dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 197th day of treatment, (b) 4 months after the third loading dose, or (c) 16 weeks after the third loading dose.WSGR Ref. No.: 47991-748.6015. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; administering to the human subject a third loading dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 113th day of treatment, (b) 2 months after the second loading dose, or (c) 8 weeks after the second loading dose; and administering to the human subject a first maintenance dose of about 25 mg to about 100 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 225th day of treatment, (b) 4 months after the third loading dose, or (c) 16 weeks after the third loading dose.

6. The dosing regimen of any one of claims 3-5, wherein the dosing regimen further comprisesadministering to the human subject one or more maintenance doses after the first maintenance dose is administered.WSGR Ref. No.: 47991-748.6017. The dosing regimen of claim 6, wherein each of the one or more maintenance doses after the firstmaintenance dose independently contains the compound at an amount of from about 25 mg to about 100 mg.

8. The dosing regimen of claim 7, wherein each of the one or more maintenance doses after the firstmaintenance dose independently contains the compound at an amount of about 45 mg.

9. The dosing regimen of claim 7, wherein each of the one or more maintenance doses after the firstmaintenance dose independently contains the compound at an amount of about 70 mg.

10. The method of claim 1 or 2 or the dosing regimen of any one of claims 3-9, wherein the compoundhas the following structure:(II).

11. The method of any one of claims 1, 2, and 10 or the dosing regimen of any one of claims 3-10,wherein the first loading dose contains the compound at an amount of about 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

12. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of about 30 mg.

13. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of about 70 mg.WSGR Ref. No.: 47991-748.60114. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of about 45 mg.

15. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of about 50 mg.

16. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 25 mg to about 35 mg.

17. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 35 mg to about 50 mg.

18. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 45 mg to about 70 mg.

19. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 50 mg to about 70 mg.

20. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 60 mg to about 80 mg.

21. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 30 mg to about 45 mg.

22. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 25 mg to about 40 mg.

23. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 35 mg to about 45 mg.

24. The method of any one of claims 1, 2, 10, and 11 or the dosing regimen of any one of claims 3-11,wherein the first loading dose contains the compound at an amount of from about 40 mg to about 55 mg.

25. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of about 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.WSGR Ref. No.: 47991-748.60126. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of about 30 mg.

27. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of about 70 mg.

28. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of about 45 mg.

29. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of about 50 mg.

30. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 25 mg to about 35 mg.

31. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 35 mg to about 50 mg.

32. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 45 mg to about 70 mg.

33. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 50 mg to about 70 mg.

34. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 60 mg to about 80 mg.

35. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 30 mg to about 45 mg.

36. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 25 mg to about 40 mg.

37. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 35 mg to about 45 mg.

38. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains the compound at an amount of from about 40 mg to about 55 mg.

39. The method of any one of claims 1, 2, and 10-24 or the dosing regimen of any one of claims 3-24,wherein the second loading dose contains same amount of the compound as the first loading dose.WSGR Ref. No.: 47991-748.60140. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of about 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

41. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of about 30 mg.

42. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of about 70 mg.

43. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of about 45 mg.

44. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of about 50 mg.

45. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 25 mg to about 35 mg.

46. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 35 mg to about 50 mg.

47. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 45 mg to about 70 mg.

48. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 50 mg to about 70 mg.

49. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 60 mg to about 80 mg.

50. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 30 mg to about 45 mg.

51. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 25 mg to about 40 mg.

52. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 35 mg to about 45 mg.WSGR Ref. No.: 47991-748.60153. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains the compound at an amount of from about 40 mg to about 55 mg.

54. The method of any one of claims 2 and 10-39 or the dosing regimen of any one of claims 3-39,wherein the third loading dose contains same amount of the compound as the first loading dose.

55. The method of any one of claims 1, 2, and 10-54 or the dosing regimen of any one of claims 3-54,wherein the first maintenance dose contains the compound at an amount of about 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

56. The method of any one of claims 1, 2, and 10-55 or the dosing regimen of any one of claims 3-55,further comprising administering one or more maintenance doses after the first maintenance dose.

57. The method or dosing regimen of claim 56, wherein each maintenance dose of the one or moremaintenance doses independently contains the compound at an amount of about 20 mg, 22.5 mg, 25 mg, 27.5 mg, 30 mg, 32.5 mg, 35 mg, 37.5 mg, 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, or 80 mg, or at least 40 mg, 42.5 mg, 45 mg, 47.5 mg, 50 mg, 52.5 mg, 55 mg, 57.5 mg, 60 mg, 62.5 mg, 65 mg, 67.5 mg, 70 mg, 72.5 mg, 75 mg, 77.5 mg, 80 mg, 82.5 mg, 85 mg, 87.5 mg, or 90 mg.

58. The method or dosing regimen of claim 56 or 57, wherein each maintenance dose of the one or moremaintenance doses is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.

59. The method of any one of claims 1, 2, and 10-58 or the dosing regimen of any one of claims 3-58,wherein each maintenance dose of the one or more maintenance doses contains same amount of the compound.

60. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of about 30 mg.

61. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of about 45 mg.

62. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of about 70 mg.

63. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 55 mg to about 70 mg.WSGR Ref. No.: 47991-748.60164. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 55 mg to about 75 mg.

65. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 55 mg to about 80 mg.

66. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 40 mg to about 70 mg.

67. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 40 mg to about 75 mg.

68. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 40 mg to about 80 mg.

69. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 65 mg to about 90 mg.

70. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 65 mg to about 95 mg.

71. The method or the dosing regimen of claim 59, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount of from about 65 mg to about 100 mg.

72. The method of any one of claims 1, 2, and 10-71 or the dosing regimen of any one of claims 3-71,wherein the first maintenance dose and each maintenance dose of the one or more maintenance doses contains same amount of the compound as the first loading dose or the second loading dose.

73. The method of any one of claims 2 and 10-71 or the dosing regimen of any one of claims 4-71,wherein the first maintenance dose and each maintenance dose of the one or more maintenance doses contains same amount of the compound as the first loading dose, the second loading dose, or the third loading dose.

74. The method of any one of claims 1, 2, and 10-71 or the dosing regimen of any one of claims 3-71,wherein the first maintenance dose and each maintenance dose of the one or more maintenance doses contain a higher amount of the compound than the first loading dose or the second loading dose.

75. The method or the dosing regimen of claim 74, wherein the first maintenance dose or eachmaintenance dose of the one and more maintenance doses contains the compound at an amount thatWSGR Ref. No.: 47991-748.601 is at least about 10%, 20%, or 30% higher than the amount in the first loading dose or the second loading dose.

76. The method or the dosing regimen of claim 74, wherein the first maintenance dose or eachmaintenance dose of the one and more maintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg higher than the amount in the first loading dose or the second loading dose.

77. The method of any one of claims 2 and 10-71 or the dosing regimen of any one of claims 4-71,wherein the first maintenance dose and each maintenance dose of the one or more maintenance doses contain a higher amount of the compound than the first loading dose, the second loading dose, or the third loading dose.

78. The method or the dosing regimen of claim 77, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount that is at least about 10%, 20%, or 30% higher than the amount in the first loading dose, the second loading dose, or the third loading dose.

79. The method or the dosing regimen of claim 77, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg higher than the amount in the first loading dose, the second loading dose, or the third loading dose.

80. The method of any one of claims 1, 2, and 10-71 or the dosing regimen of any one of claims 3-71,wherein the first maintenance dose and each maintenance dose of the one or more maintenance doses contain a lower amount of the compound than the first loading dose or the second loading dose.

81. The method or the dosing regimen of claim 80, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount that is at least about 10%, 20%, or 30% lower than the amount in the first loading dose or the second loading dose.

82. The method or the dosing regimen of claim 80, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg lower than the amount in the first loading dose or the second loading dose.

83. The method of any one of claims 2 and 10-71 or the dosing regimen of any one of claims 4-71,wherein the first maintenance dose and each maintenance dose of the one or more maintenance doses contain a lower amount of the compound than the first loading dose, the second loading dose, or the third loading dose.

84. The method or the dosing regimen of claim 83, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount that is at least about 10%, 20%, or 30% lower than the amount in the first loading dose, the second loading dose, or the third loading dose.WSGR Ref. No.: 47991-748.60185. The method or the dosing regimen of claim 83, wherein the first maintenance dose and eachmaintenance dose of the one or more maintenance doses contains the compound at an amount that is at least about 5 mg, 10 mg, 15 mg, 20 mg, or 30 mg lower than the amount in the first loading dose, the second loading dose, or the third loading dose.

86. The method of any one of claims 1, 2, and 10-85 or the dosing regimen of any one of claims 3-85,wherein the second loading dose is administered from 4 weeks to 11 weeks, from 4 weeks to 10 weeks, from 4 weeks to 9 weeks, from 4 weeks to 8 weeks, from 4 weeks to 7 weeks, from 4 weeks to 6 weeks, from 4 weeks to 5 weeks, from 5 weeks to 12 weeks, from 5 weeks to 11 weeks, from 5 weeks to 10 weeks, from 5 weeks to 9 weeks, from 5 weeks to 8 weeks, from 5 weeks to 7 weeks, from 5 weeks to 6 weeks, from 6 weeks to 12 weeks, from 6 weeks to 11 weeks, from 6 weeks to 10 weeks, from 6 weeks to 9 weeks, from 6 weeks to 8 weeks, from 6 weeks to 7 weeks, from 7 weeks to 12 weeks, from 7 weeks to 11 weeks, from 7 weeks to 10 weeks, from 7 weeks to 9 weeks, from 7 weeks to 8 weeks, from 8 weeks to 12 weeks, from 8 weeks to 11 weeks, from 8 weeks to 10 weeks, from 8 weeks to 9 weeks, from 9 weeks to 12 weeks, from 9 weeks to 11 weeks, from 9 weeks to 10 weeks, from 10 weeks to 12 weeks, from 10 weeks to 11 weeks, or from 11 weeks to 12 weeks after the first loading dose.

87. The method of any one of claims 1, 2, and 10-85 or the dosing regimen of any one of claims 3-85,wherein the second loading dose is administered about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks after the first loading dose.

88. The method of any one of claims 1, 2, and 10-85 or the dosing regimen of any one of claims 3-85,wherein the second loading dose is administered about 6 weeks after the administration of the first loading dose.

89. The method of any one of claims 1, 2, and 10-85 or the dosing regimen of any one of claims 3-85,wherein the second loading dose is administered about 7 weeks after the administration of the first loading dose.

90. The method of any one of claims 1, 2, and 10-85 or the dosing regimen of any one of claims 3-85,wherein the second loading dose is administered about 8 weeks after the administration of the first loading dose.

91. The method of any one of claims 1, 2, and 10-85 or the dosing regimen of any one of claims 3-85,wherein the second loading dose is administered about 9 weeks after the administration of the first loading dose.

92. The method of any one of claims 1, 2, and 10-85 or the dosing regimen of any one of claims 3-85,wherein the second loading dose is administered about 10 weeks after the administration of the first loading dose.

93. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered from 4 weeks to 11 weeks, from 4 weeks to 10 weeks, from 4 weeks to 9 weeks, from 4 weeks to 8 weeks, from 4 weeks to 7 weeks, from 4 weeks to 6 weeks, from 4 weeks to 5 weeks, from 5 weeks to 12 weeks, from 5 weeks to 11 weeks, from 5WSGR Ref. No.: 47991-748.601 weeks to 10 weeks, from 5 weeks to 9 weeks, from 5 weeks to 8 weeks, from 5 weeks to 7 weeks, from 5 weeks to 6 weeks, from 6 weeks to 12 weeks, from 6 weeks to 11 weeks, from 6 weeks to 10 weeks, from 6 weeks to 9 weeks, from 6 weeks to 8 weeks, from 6 weeks to 7 weeks, from 7 weeks to 12 weeks, from 7 weeks to 11 weeks, from 7 weeks to 10 weeks, from 7 weeks to 9 weeks, from 7 weeks to 8 weeks, from 8 weeks to 12 weeks, from 8 weeks to 11 weeks, from 8 weeks to 10 weeks, from 8 weeks to 9 weeks, from 9 weeks to 12 weeks, from 9 weeks to 11 weeks, from 9 weeks to 10 weeks, from 10 weeks to 12 weeks, from 10 weeks to 11 weeks, or from 11 weeks to 12 weeks after the second loading dose.

94. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks after the second loading dose.

95. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 4 weeks after the administration of the second loading dose.

96. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 5 weeks after the administration of the second loading dose.

97. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 6 weeks after the administration of the second loading dose.

98. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 7 weeks after the administration of the second loading dose.

99. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 8 weeks after the administration of the second loading dose.

100. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 9 weeks after the administration of the second loading dose.

101. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the third loading dose is administered about 10 weeks after the administration of the second loading dose.

102. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the first loading dose, the second loading dose, and the third loading dose are administered about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks apart from each other.WSGR Ref. No.: 47991-748.601103. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the first loading dose, the second loading dose, and the third loading dose are administered about 6 weeks apart from each other.

104. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the first loading dose, the second loading dose, and the third loading dose are administered about 7 weeks apart from each other.

105. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the first loading dose, the second loading dose, and the third loading dose are administered about 8 weeks apart from each other.

106. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the first loading dose, the second loading dose, and the third loading dose are administered about 9 weeks apart from each other.

107. The method of any one of claims 2 and 10-92 or the dosing regimen of any one of claims 4-92,wherein the first loading dose, the second loading dose, and the third loading dose are administered about 10 weeks apart from each other.

108. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered from 8 weeks to 11 months, from 8 weeks to 10 months, from 8 weeks to 8 months, from 8 weeks to 6 months, from 8 weeks to 20 weeks, from 8 weeks to 16 weeks, from 8 weeks to 14 weeks, from 8 weeks to 12 weeks, from 8 weeks to 10 weeks, from 10 weeks to 12 weeks, from 12 weeks to 16 weeks, from 12 weeks to 12 months, from 12 weeks to 11 months, from 12 weeks to 12 months, from 12 weeks to 8 months, from 12 weeks to 6 months, from 12 weeks to 20 weeks, from 12 weeks to 16 weeks, from 12 weeks to 14 weeks, from 16 weeks to 12 months, from 16 weeks to 11 months, from 16 weeks to 10 months, from 16 weeks to 8 months, from 16 weeks to 6 months, from 16 weeks to 20 weeks, from 20 weeks to 12 months, from 20 weeks to 11 months, from 20 weeks to 10 months, from 20 weeks to 8 months, from 20 weeks to 6 months, from 6 months to 12 months, from 6 months to 11 months, from 6 months to 10 months, from 6 months to 9 months, from 6 months to 8 months, from 6 months to 7 months, from 7 months to 12 months, from 7 months to 11 months, from 7 months to 10 months, from 7 months to 9 months, from 7 months to 8 months, from 8 months to 12 months, from 8 months to 11 months, from 8 months to 10 months, from 8 months to 9 months, from 9 months to 12 months, from 9 months to 11 months, from 9 months to 10 months, from 10 months to 12 months, from 10 months to 11 months, or from 11 months to 12 months after the second loading dose.

109. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 22 weeks, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months after the second loading dose.WSGR Ref. No.: 47991-748.601110. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 8 weeks after the second loading dose.

111. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 12 weeks after the second loading dose.

112. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 16 weeks after the second loading dose.

113. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 20 weeks after the second loading dose.

114. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 4 months after the second loading dose.

115. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 6 months after the second loading dose.

116. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 9 months after the second loading dose.

117. The method of any one of claims 1 and 10-107 or the dosing regimen of any one of claims 3 and 6-107, wherein the first maintenance dose is administered about 12 months after the second loading dose.

118. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered from 8 weeks to 11 months, from 8 weeks to 10 months, from 8 weeks to 8 months, from 8 weeks to 6 months, from 8 weeks to 20 weeks, from 8 weeks to 16 weeks, from 8 weeks to 14 weeks, from 8 weeks to 12 weeks, from 8 weeks to 10 weeks, from 10 weeks to 12 weeks, from 12 weeks to 16 weeks, from 12 weeks to 12 months, from 12 weeks to 11 months, from 12 weeks to 12 months, from 12 weeks to 8 months, from 12 weeks to 6 months, from 12 weeks to 20 weeks, from 12 weeks to 16 weeks, from 12 weeks to 14 weeks, from 16 weeks to 12 months, from 16 weeks to 11 months, from 16 weeks to 10 months, from 16 weeks to 8 months, from 16 weeks to 6 months, from 16 weeks to 20 weeks, from 20 weeks to 12 months, from 20 weeks to 11 months, from 20 weeks to 10 months, from 20 weeks to 8 months, from 20 weeks to 6 months, from 6 months to 12 months, from 6 months to 11 months, from 6 months to 10 months, from 6 months to 9 months, from 6 months to 8 months, from 6 months to 7 months, from 7 months to 12 months, from 7 months to 11 months, from 7 months to 10 months, from 7 months to 9 months, from 7 months to 8 months, from 8 months to 12 months, from 8 months to 11 months, from 8 months to 10 months, from 8 months to 9 months, from 9 months to 12WSGR Ref. No.: 47991-748.601 months, from 9 months to 11 months, from 9 months to 10 months, from 10 months to 12 months, from 10 months to 11 months, or from 11 months to 12 months after the third loading dose.

119. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 22 weeks, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months after the third loading dose.

120. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 8 weeks after the third loading dose.

121. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 12 weeks after the third loading dose.

122. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 16 weeks after the third loading dose.

123. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 20 weeks after the third loading dose.

124. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 4 months after the third loading dose.

125. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 6 months after the third loading dose.

126. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 9 months after the third loading dose.

127. The method of any one of claims 2 and 10-107 or the dosing regimen of any one of claims 4-107,wherein the first maintenance dose is administered about 12 months after the third loading dose.

128. The method of any one of claims 1, 2, and 10-107 or the dosing regimen of any one of claims 3-107,wherein the one or more maintenance doses consist of one maintenance dose.

129. The method of any one of claims 1, 2, and 10-107 or the dosing regimen of any one of claims 3-107,wherein the one or more maintenance doses comprise at least two maintenance doses, and wherein each maintenance dose of the one or more maintenance doses other than the first maintenance dose is administered independently from 8 weeks to 11 months, from 8 weeks to 10 months, from 8 weeks to 8 months, from 8 weeks to 6 months, from 8 weeks to 20 weeks, from 8 weeks to 16 weeks, from 8 weeks to 14 weeks, from 8 weeks to 12 weeks, from 8 weeks to 10 weeks, from 10 weeks to 12 weeks, from 12 weeks to 16 weeks, from 12 weeks to 12 months, from 12 weeks to 11 months, from 12 weeks to 12 months, from 12 weeks to 8 months, from 12 weeks to 6 months, from 12 weeks to 20 weeks, from 12 weeks to 16 weeks, from 12 weeks to 14 weeks, from 16 weeks to 12 months, from 16 weeks to 11 months, from 16 weeks to 10 months, from 16 weeks to 8 months, from 16 weeks to 6 months, from 16 weeks to 20 weeks, from 20 weeks to 12 months, from 20 weeks to 11 months, from 20 weeks to 10 months, from 20 weeks to 8 months, from 20 weeks to 6 months, from 6 months to 12 months, from 6 months to 11 months, from 6 months to 10 months,WSGR Ref. No.: 47991-748.601 from 6 months to 9 months, from 6 months to 8 months, from 6 months to 7 months, from 7 months to 12 months, from 7 months to 11 months, from 7 months to 10 months, from 7 months to 9 months, from 7 months to 8 months, from 8 months to 12 months, from 8 months to 11 months, from 8 months to 10 months, from 8 months to 9 months, from 9 months to 12 months, from 9 months to 11 months, from 9 months to 10 months, from 10 months to 12 months, from 10 months to 11 months, or from 11 months to 12 months after the dose immediately preceding the respective maintenance dose.

130. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered independently about 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 22 weeks, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months after the dose immediately preceding the respective maintenance dose.

131. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 8 weeks after the dose immediately preceding the respective maintenance dose.

132. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 12 weeks after the dose immediately preceding the respective maintenance dose.

133. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 16 weeks after the dose immediately preceding the respective maintenance dose.

134. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 20 weeks after the dose immediately preceding the respective maintenance dose.

135. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 4 months after the dose immediately preceding the respective maintenance dose.

136. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 6 months after the dose immediately preceding the respective maintenance dose.

137. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 9 months after the dose immediately preceding the respective maintenance dose.

138. The method or the dosing regimen of claim 129, wherein each maintenance dose of the one or moremaintenance doses other than the first maintenance dose is administered about 12 months after the dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601139. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the one or more maintenance doses consist of two maintenance doses.

140. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the one or more maintenance doses consist of three maintenance doses.

141. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the one or more maintenance doses consist of four maintenance doses.

142. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the one or more maintenance doses consist of five, six, seven, eight, or more maintenance doses.

143. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the one or more maintenance doses comprise more than three maintenance doses.

144. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the one or more maintenance doses are administered over a lifetime of the human subject.

145. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the method or the dosing regimen comprises administering the one or more maintenance doses to the human subject until an indication that a most recent maintenance dose is not tolerated by the human subject.

146. The method of any one of claims 1, 2, and 10-138 or the dosing regimen of any one of claims 3-138,wherein the one or more maintenance doses are administered to the human subject over a period of at least one year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 15 years, 20 years, 25 years, 30 years, 35, years, 40 years, 45 years, 50 years, 55 years, or 60 years.

147. The method of any one of claims 1 and 10-146 or the dosing regimen of any one of claims 3 and 6-146, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg.

148. The method of any one of claims 1 and 10-146 or the dosing regimen of any one of claims 3 and 6-146, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 70 mg.

149. The method of any one of claims 2 and 10-146 or the dosing regimen of any one of claims 4-146,wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 70 mg.

150. The method of any one of claims 2 and 10-146 or the dosing regimen of any one of claims 4-146,wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg.WSGR Ref. No.: 47991-748.601151. The method of any one of claims 1 and 10-146 or the dosing regimen of any one of claims 3 and 6-146, wherein the second loading dose is administered about 8 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose of the after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

152. The method of any one of claims 2 and 10-146 or the dosing regimen of any one of claims 4-146,wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 4 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

153. The method or the dosing regimen of any one of claims 139-146, wherein the one or moremaintenance doses are administered at a same dose frequency or a substantially same dose frequency.

154. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof,WSGR Ref. No.: 47991-748.601 wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.

155. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601156. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601157. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, and each maintenance dose of the one or more maintenance doses is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.

158. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the one or more maintenance doses is about 30 mg.

159. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the one or more maintenance doses is about 45 mg.

160. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the one or more maintenance doses is about 50 mg.

161. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the one or more maintenance doses is about 60 mg.WSGR Ref. No.: 47991-748.601162. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the one or more maintenance doses is about 70 mg.

163. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose and the second loading dose is about 30 mg, and the amount of the compound in each of the one or more maintenance doses is about 25 mg.

164. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose and the second loading dose is about 45 mg, and the amount of the compound in each of the one or more maintenance doses is about 30 mg.

165. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose and the second loading dose is about 50 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg.

166. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose and the second loading dose is about 60 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg.

167. The method of any one of claims 154-157, wherein the amount of the compound in each dose of thefirst loading dose and the second loading dose is about 70 mg, and the amount of the compound in each of the one or more maintenance doses is about 45 mg.

168. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:WSGR Ref. No.: 47991-748.601 (I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.

169. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose,WSGR Ref. No.: 47991-748.601 wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 8 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

170. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg,WSGR Ref. No.: 47991-748.601 wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 10 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.

171. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 12 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 6 months after the third loading dose, and each maintenance after the first maintenance dose is administeredWSGR Ref. No.: 47991-748.601 independently about 6 months after a dose immediately preceding the respective maintenance dose.

172. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 3 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601173. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 4 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601174. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 5 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the third loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601175. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses contains the compound at an amount of from about 30 mg to about 80 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered about 6 months after the third loading dose, and each maintenance after the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601176. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 30 mg.

177. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 45 mg.

178. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 50 mg.

179. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 60 mg.

180. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses is about 70 mg.

181. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the third loading dose is about 30 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 25 mg.

182. The method of any one of claims 168-175, wherein the amount of the compound in each dose of theamount of the compound in each of the first loading dose, the second loading dose, and the third loading dose is about 45 mg, and the first maintenance dose and the one or more maintenance doses is about 40 mg.

183. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the third loading dose is about 50 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 45 mg.

184. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the third loading dose is about 60 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 45 mg.

185. The method of any one of claims 168-175, wherein the amount of the compound in each dose of thefirst loading dose, the second loading dose, and the third loading dose is about 70 mg, and the amount of the compound in each of the first maintenance dose and the one or more maintenance doses is about 45 mg.WSGR Ref. No.: 47991-748.601186. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601187. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601188. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601189. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 6 months after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601190. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601191. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 8 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601192. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 10 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601193. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 12 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601194. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 3 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601195. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 4 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601196. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 5 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601197. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, the first maintenance dose and the one or more maintenance doses contains the compound at an amount of about 70 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601198. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 12 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601199. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601200. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 20 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601201. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 6 months after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601202. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601203. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 8 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601204. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 10 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601205. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 12 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601206. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 6 weeks after the first loading dose, the third loading dose is administered about 3 weeks after the second loading dose, the first maintenance dose is administered about 12 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 12 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601207. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the third loading dose is administered about 4 weeks after the second loading dose, the first maintenance dose is administered about 16 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601208. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 10 weeks after the first loading dose, the third loading dose is administered about 5 weeks after the second loading dose, the first maintenance dose is administered about 20 weeks after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 20 weeks after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601209. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, a first maintenance dose following the third loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose, the second loading dose and the third loading dose contains the compound at an amount of about 70 mg, wherein the first maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 12 weeks after the first loading dose, the third loading dose is administered about 6 weeks after the second loading dose, the first maintenance dose is administered about 6 months after the third loading dose, and each maintenance dose of the one or more maintenance doses following the first maintenance dose is administered independently about 6 months after a dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601210. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; and administering to the human subject a first maintenance dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 169th day of treatment, (b) 4 months after the second loading dose, or (c) 16 weeks after the second loading dose.WSGR Ref. No.: 47991-748.601211. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; and administering to the human subject a first maintenance dose of about 45 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 169th day of treatment, (b) 4 months after the second loading dose, or (c) 16 weeks after the second loading dose.WSGR Ref. No.: 47991-748.601212. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 85th day of treatment, (b) 1 month after the second loading dose, or (c) 4 weeks after the second loading dose; and administering to the human subject a first maintenance dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 197th day of treatment, (b) 4 months after the third loading dose, or (c) 16 weeks after the third loading dose.WSGR Ref. No.: 47991-748.601213. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 85th day of treatment, (b) 1 month after the second loading dose, or (c) 4 weeks after the second loading dose; and administering to the human subject a first maintenance dose of about 45 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 197th day of treatment, (b) 4 months after the third loading dose, or (c) 16 weeks after the third loading dose.WSGR Ref. No.: 47991-748.601214. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 113th day of treatment, (b) 2 months after the second loading dose, or (c) 8 weeks after the second loading dose; and administering to the human subject a first maintenance dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 225th day of treatment, (b) 4 months after the third loading dose, or (c) 16 weeks after the third loading dose.WSGR Ref. No.: 47991-748.601215. A dosing regimen for administering a compound according to the following chemical structure:(I), or a salt thereof to a human subject in need of treatment for a disease or condition characterized by a reduced expression or function of NaV1.1 protein, wherein the dosing regimen comprises: administering to the human subject a first loading dose of from about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition on the first day of treatment; administering to the human subject a second loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 57th day of treatment, (b) 2 months after the first loading dose, or (c) 8 weeks after the first loading dose; administering to the human subject a third loading dose of about 70 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 113th day of treatment, (b) 2 months after the second loading dose, or (c) 8 weeks after the second loading dose; and administering to the human subject a first maintenance dose of about 45 mg of the compound of formula (I) or a salt thereof in a pharmaceutical composition (a) on the 225th day of treatment, (b) 4 months after the third loading dose, or (c) 16 weeks after the third loading dose.WSGR Ref. No.: 47991-748.601216. The method of any one of claims 154-209 or the dosing regimen of any one of claims 210-215,wherein the compound has the following structure:(II).

217. The method of any one of claims 1, 2, 10-209, and 216 or the dosing regimen of any one of claims3-153 and 210-216, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient, carrier, or diluent.

218. The method of any one of claims 1, 2, 10-209, and 216 or the dosing regimen of any one of claims3-153 and 210-217, wherein the pharmaceutical composition is a liquid composition.

219. The method or the dosing regimen of claim 218, wherein the pharmaceutical composition comprisesfrom 0.1 mL to 50 mL of a diluent, and wherein the compound is solubilized or diluted in the diluent.

220. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises about 0.1 mL, 0.5 mL, 1 mL, 2 mL, 2.5 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, 13 mL, 14 mL, 15 mL, 16 mL, 17 mL, 18 mL, 19 mL, 20 mL, 25 mL, 30 mL, 35 mL, 40 mL, 45 mL, or 50 mL of the diluent.

221. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises 1 mL to 20 mL of the diluent, 2 mL to 10 mL of the diluent, or 1 mL to 5 mL of the diluent.

222. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises at least 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, or 10 mL of the diluent.WSGR Ref. No.: 47991-748.601223. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises about 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, or 10 mL of the diluent.

224. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises about 4 mL of the diluent.

225. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises about 7 mL of the diluent.

226. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises about 9 mL of the diluent.

227. The method or the dosing regimen of any one of claims 217-219, wherein the pharmaceuticalcomposition comprises about 10 mL of the diluent.

228. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and the first loading dose has volume of 10 mL or higher.

229. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and the first loading dose has volume of 5 mL or higher.

230. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and the first loading dose has volume of about 10 mL.

231. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and the first loading dose has volume of about 15 mL.

232. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and the first loading dose has volume of about 20 mL.

233. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and the first loading dose has volume of about 25 mL.

234. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and the first loading dose has volume of about 30 mL.

235. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of 5 mL or higher.

236. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of 10 mL or higher.

237. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of about 5 mL.

238. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of about 10 mL.WSGR Ref. No.: 47991-748.601239. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of about 15 mL.

240. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of about 20 mL.

241. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of about 25 mL.

242. The method or the dosing regimen of any one of claims 217-219, wherein the compound isdissolved or diluted in the diluent and each maintenance dose of the one or more maintenance doses has a volume of about 30 mL.

243. The method or the dosing regimen of any one of claims 217-242, wherein the diluent comprises acerebral spinal fluid (CSF) sample from the subject or an artificial cerebral spinal fluid (aCSF) solution.

244. The method or the dosing regimen of claim 243, wherein the diluent is the aCSF solution that lackssodium phosphate.

245. The method or the dosing regimen of claim 243, wherein each dose of the pharmaceuticalcomposition comprises 10 mL of the diluent.

246. The method or the dosing regimen of any one of claims 217-245, wherein the diluent is an isotonicsolution.

247. The method or the dosing regimen of any one of claims 217-245, wherein the diluent is a solutionwith at least pH 5.8.

248. The method or the dosing regimen of any one of claims 217-245, wherein the diluent is a solutionwith pH 6.6 – 7.6.

249. The method or the dosing regimen of any one of claims 217-248, wherein the diluent is a buffercomprising 25-250 mM NaCl.

250. The method or the dosing regimen of any one of claims 217-249, wherein the diluent is a buffercomprising 0.1-20 mM KCl.

251. The method or the dosing regimen of any one of claims 217-243 and 245-250, wherein the diluent isa buffer comprising 0.1-50 mM Na2HPO4.

252. The method or the dosing regimen of any one of claims 217-243 and 245-250, wherein the diluent isa buffer comprising 0.1-50 mM NaH2PO4.

253. The method or the dosing regimen of any one of claims 217-252, wherein the diluent is a buffercomprising 0.1-50 mM CaCl2.

254. The method or the dosing regimen of any one of claims 217-253, wherein the diluent is a buffercomprising 0.1-50 mM MgCl2.WSGR Ref. No.: 47991-748.601255. The method or the dosing regimen of any one of claims 217-243 and 245-254, wherein the diluent isa buffer comprising 150 mM NaCl, 3.0 mM KCl, 0.7 mM Na2HPO4, 0.3 mM NaH2PO4, 0.79 mM MgCl2, and 1.4 mM CaCl2.

256. The method or the dosing regimen of any one of claims 217-255, wherein the diluent is a bufferfurther comprising 1-100 mM NaHCO3, 1-100 mM KHCO3, or a combination thereof.

257. The method or the dosing regimen of any one of claims 217-256, wherein the diluent furthercomprises carbohydrates.

258. The method or the dosing regimen of claim 257, wherein the carbohydrates comprise D-glucose.

259. The method or the dosing regimen of claim 257, wherein the diluent comprises 1-100 mM D-glucose.

260. The method of any one of claims 1, 2, 10-209, and 216-259 or the dosing regimen of any one ofclaims 3-153, and 210-259, wherein the pharmaceutical composition comprises 0.1-50 mM CaCl2or CaCl2·2H2O.

261. The method or the dosing regimen of claim 260, wherein the pharmaceutical composition comprises1-2 mM CaCl2or CaCl2·2H2O.

262. The method or the dosing regimen of claim 260, wherein the pharmaceutical composition comprisesabout 1.4 mM CaCl2or CaCl2·2H2O.

263. The method of any one of claims 1, 2, 10-209, and 216-262 or the dosing regimen of any one ofclaims 3-153, and 210-262, wherein the pharmaceutical composition further comprises 0.1-50 mM MgCl2or MgCl2·6H2O.

264. The method or the dosing regimen of claim 263, wherein the pharmaceutical composition comprises0.5-1.5 mM MgCl2or MgCl2·6H2O.

265. The method or the dosing regimen of claim 263, wherein the pharmaceutical composition comprisesabout 0.79 mM MgCl2or MgCl2·6H2O.

266. The method of any one of claims 1, 2, 10-209, and 216-265 or the dosing regimen of any one ofclaims 3-153 and 210-265, wherein the pharmaceutical composition comprises 5-250 mM NaCl, 0.1-20 mM KCl, 0.1-50 mM CaCl2or CaCl2·2H2O, and 0.1-50 mM MgCl2or MgCl2·6H2O.

267. The method of any one of claims 1, 2, 10-209, and 216-265 or the dosing regimen of any one ofclaims 3-153 and 210-265, wherein the pharmaceutical composition comprises the compound at a concentration of about 0.1 mg / mL to about 500 mg / mL, (a) calcium chloride (CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) at a concentration of about 0.1 mM to about 50 mM; (b) magnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) at a concentration of about 0.1 mM to about 50 mM; (c) potassium chloride (KCl) at a concentration of about 0.1 mM to about 20 mM; (d) sodium chloride (NaCl) at a concentration of about 25 mM to about 250 mM; and (e) water.WSGR Ref. No.: 47991-748.601268. The method or the dosing regimen of claim 267, wherein the concentration of calcium chloride(CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) is 0.2 mM to 25 mM, 0.5 mM to 10 mM, 0.75 mM to 5 mM, or 1 mM to 2 mM.

269. The method or the dosing regimen of claim 267, wherein the concentration of calcium chloride(CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) is from about 1 mM to about 2 mM.

270. The method or the dosing regimen of claim 267, wherein the concentration of calcium chloride(CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) is about 1.4 mM.

271. The method or the dosing regimen of any one of claims 267-270, wherein the concentration ofmagnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) is 0.2 mM to 25 mM, 0.3 mM to 15 mM, 0.4 mM to 5 mM, 0.5 mM to 1.5 mM, or 0.6 mM to 1 mM.

272. The method or the dosing regimen of any one of claims 267-270, wherein the concentration ofmagnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) is from about 0.6 mM to about 1 mM.

273. The method or the dosing regimen of any one of claims 267-270, wherein the concentration ofmagnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) is about 0.79 mM.

274. The method or the dosing regimen of any one of claims 267-273, wherein the concentration ofpotassium chloride is 0.5 mM to 10 mM, 1 mM to 7.5 mM, or 2 mM to 5 mM.

275. The method or the dosing regimen of any one of claims 267-273, wherein the concentration ofpotassium chloride is from about 2 mM to about 5 mM.

276. The method or the dosing regimen of any one of claims 267-273, wherein the concentration ofpotassium chloride is about 3 mM.

277. The method or the dosing regimen of any one of claims 267-276, wherein the concentration ofsodium chloride is 25 mM to 250 mM, 100 mM to 160 mM, 110 mM to 140 mM, or 130 mM to 160 mM.

278. The method or the dosing regimen of any one of claims 267-276, wherein the concentration ofsodium chloride is from about 125 mM to 145 mM.

279. The method or the dosing regimen of any one of claims 267-276, wherein the concentration ofsodium chloride is about 130 mM.

280. The method or the dosing regimen of any one of claims 267-276, wherein the concentration ofsodium chloride is from about 140 mM to 160 mM.

281. The method or the dosing regimen of any one of claims 267-276, wherein the concentration ofsodium chloride is about 150 mM.

282. The method or the dosing regimen of any one of claims 267-281, wherein:the concentration of the compound is about 3 mg / mL, about 4.5 mg / mL, about 7 mg / mL, or about 33 mg / mL; (i) the concentration of calcium chloride dihydrate is about 1.4 mM;(ii) the concentration of magnesium chloride hexahydrate is about 0.79 mM;(iii) the concentration of potassium chloride is about 3 mM; andWSGR Ref. No.: 47991-748.601 (iv) the concentration of sodium chloride is about 150 mM.

283. The method of any one of claims 1, 2, 10-209, and 216-265 or the dosing regimen of any one ofclaims 3-153 and 210-265, wherein the pharmaceutical composition comprises the compound at a concentration of about 0.1 mg / mL to about 500 mg / mL, (a) calcium ion (Ca2+) at a concentration of about 0.1 mM to about 50 mM; (b) magnesium ion (Mg2+) at a concentration of about 0.1 mM to about 50 mM; (c) potassium ion (K+) at a concentration of about 0.1 mM to about 20 mM; (d) sodium ion (Na+) at a concentration of about 25 mM to about 250 mM; (e) chloride ion (Cl-) at a concentration of about 25 mM to about 250 mM; and (f) water.

284. The method of any one of claims 1, 2, 10-209, and 216-265 or the dosing regimen of any one ofclaims 3-153 and 210-265, wherein the pharmaceutical composition comprises the compound at a concentration of about 0.1 mg / mL to about 500 mg / mL, (a) calcium ion (Ca2+) at a concentration of about 1.4 mM; (b) magnesium ion (Mg2+) at a concentration of about 0.79 mM; (c) potassium ion (K+) at a concentration of about 3 mM; (d) sodium ion (Na+) at a concentration of about 160 mM; (e) chloride ion (Cl-) at a concentration of about 160 mM; and (f) water.

285. The method or the dosing regimen of any one of claims 260-284, wherein the pharmaceuticalcomposition lacks Na2HPO4and / or NaH2PO4.

286. The method or the dosing regimen of any one of claims 260-285, wherein the pharmaceuticalcomposition lacks phosphate ion.

287. The method or the dosing regimen of any one of claims 260-286, wherein each dose of thepharmaceutical composition comprises 10 mL of the diluent.

288. The method or the dosing regimen of any one of claims 217-287, wherein the diluent furthercomprises an antioxidant.

289. The method or the dosing regimen of claim 288, wherein the antioxidant is t-butylhydroxyquinoline(TBHQ), butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), vitamin E, or any combination thereof.

290. The method of any one of claims 1, 2, 10-209, and 216-289 or the dosing regimen of any one ofclaims 3-153 and 210-289, wherein the pharmaceutical composition is administered into the intrathecal space of the human subject.

291. The method of any one of claims 1, 2, 10-209, and 216-289 or the dosing regimen of any one ofclaims 3-153 and 210-289, wherein the pharmaceutical composition is administered into the cerebrospinal fluid of the human subject.WSGR Ref. No.: 47991-748.601292. The method of any one of claims 1, 2, 10-209, and 216-289 or the dosing regimen of any one ofclaims 3-153 and 210-289, wherein the pharmaceutical composition is administered into the brain of the human subject.

293. The method of any one of claims 1, 2, 10-209, and 216-289 or the dosing regimen of any one ofclaims 3-153 and 210-289, wherein the pharmaceutical composition is administered into the cerebrospinal fluid in the brain of the human subject.

294. The method of any one of claims 1, 2, 10-209, and 216-293 or the dosing regimen of any one ofclaims 3-153 and 210-293, wherein the pharmaceutical composition is administered as a bolus injection.

295. The method or the dosing regimen of claim 294, wherein the method or the dosing regimencomprises administering the pharmaceutical composition as a bolus injection over 1 to 60 minutes, 1 to 50 minutes, 1 to 40 minutes, 1 to 30 minutes, 1 to 20 minutes, 1 to 10 minutes, 1 to 5 minutes, or 1 to 3 minutes.

296. The method of any one of claims 1, 2, 10-209, and 216-293 or the dosing regimen of any one ofclaims 3-153 and 210-293, wherein the pharmaceutical composition is administered by infusion with a delivery pump.

297. The method of any one of claims 1, 2, 10-209, and 216-293 or the dosing regimen of any one ofclaims 3-153 and 210-293, wherein the pharmaceutical composition is administered by intracerebroventricular injection.

298. The method of any one of claims 1, 2, 10-209, and 216-293 or the dosing regimen of any one ofclaims 3-153 and 210-293, wherein the pharmaceutical composition is administered by intrathecal injection.

299. The method or dosing regimen of claim 298, wherein each dose of the pharmaceutical compositioncomprises a diluent of a volume of 10 mL, and the diluent is an aCSF solution that lacks sodium phosphate.

300. The method of any one of claims 1, 2, 10-209, and 216-293 or the dosing regimen of any one ofclaims 3-153 and 210-293, wherein the pharmaceutical composition is administered by lumbar injection.

301. The method of any one of claims 1, 2, 10-209, and 216-300 or the dosing regimen of any one ofclaims 3-153 and 210-300, wherein the pharmaceutical composition does not comprise a preservative.

302. The method of any one of claims 1, 2, 10-209, and 216-300 or the dosing regimen of any one ofclaims 3-153 and 210-300, wherein the concentration of the compound in the pharmaceutical composition is about 0.1 mg / mL to about 250 mg / mL.

303. The method of any one of claims 1, 2, 10-209, and 216-300 or the dosing regimen of any one ofclaims 3-153 and 210-300, wherein the concentration of the compound in the pharmaceutical composition is from 6.7 mg / mL to 188 mg / mL, from 6.8 mg / mL to 187 mg / mL, from 3 mg / mL to 100 mg / mL, or from 3 mg / mL to 33 mg / mL.WSGR Ref. No.: 47991-748.601304. The method of any one of claims 1, 2, 10-209, and 216-300 or the dosing regimen of any one ofclaims 3-153 and 210-300, wherein the concentration of the compound in the pharmaceutical composition is about 0.1 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 2.5 mg / mL, 3 mg / mL, 4 mg / mL, 4.5 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 8 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 17 mg / mL, 18 mg / mL, 19 mg / mL, 20 mg / mL, 22 mg / mL, 25 mg / mL, 28 mg / mL, or 33 mg / mL.

305. The method of any one of claims 1, 2, 10-209, and 216-300 or the dosing regimen of any one ofclaims 3-153 and 210-300, wherein the concentration of the compound in the pharmaceutical composition is 11 mg / mL, 22 mg / mL, 33 mg / mL, 44 mg / mL, 55 mg / mL, 66 mg / mL, 77 mg / mL, 88 mg / mL, 99 mg / mL, or 100 mg / mL.

306. The method of any one of claims 1, 2, 10-209, and 216-300 or the dosing regimen of any one ofclaims 3-153 and 210-300, wherein the concentration of the compound in the pharmaceutical composition is about 3 mg / mL, 4 mg / mL, 4.5 mg / mL, 5 mg / mL, 6 mg / mL, 7 mg / mL, 9 mg / mL, 10 mg / mL, 11 mg / mL, 12 mg / mL, 13 mg / mL, 14 mg / mL, 15 mg / mL, 16 mg / mL, 17 mg / mL, 18 mg / mL, 19 mg / mL, 20 mg / mL, 22.5 mg / mL, 25 mg / mL, 27.5 mg / mL, 30 mg / mL, 32.5 mg / mL, 35 mg / mL, 37.5 mg / mL, 40 mg / mL, 42.5 mg / mL, 45 mg / mL, 47.5 mg / mL, 50 mg / mL, 52.5 mg / mL, 55 mg / mL, 57.5 mg / mL, 60 mg / mL, 62.5 mg / mL, 65 mg / mL, 67.5 mg / mL, 70 mg / mL, 72.5 mg / mL, 75 mg / mL, 77.5 mg / mL, 80 mg / mL, 82.5 mg / mL, 85 mg / mL, 87.5 mg / mL, 90 mg / mL, 92.5 mg / mL, 95 mg / mL, 97.5 mg / mL, 100 mg / mL, 102.5 mg / mL, 105 mg / mL, 107.5 mg / mL, 110 mg / mL, 112.5 mg / mL, 115 mg / mL, 117.5 mg / mL, 120 mg / mL, 122.5 mg / mL, 125 mg / mL, 127.5 mg / mL, 130 mg / mL, 132.5 mg / mL, 135 mg / mL, 137.5 mg / mL, 140 mg / mL, 142.5 mg / mL, 145 mg / mL, 147.5 mg / mL, 150 mg / mL, 152.5 mg / mL, 155 mg / mL, 157.5 mg / mL, 160 mg / mL, 162.5 mg / mL, 165 mg / mL, 167.5 mg / mL, 170 mg / mL, 172.5 mg / mL, 175 mg / mL, 177.5 mg / mL, 180 mg / mL, 182.5 mg / mL, 185 mg / mL, 187.5 mg / mL, 190 mg / mL, 192.5 mg / mL, 195 mg / mL, 197.5 mg / mL, 200 mg / mL, 202.5 mg / mL, 205 mg / mL, 207.5 mg / mL, 210 mg / mL, 212.5 mg / mL, 215 mg / mL, 217.5 mg / mL, 220 mg / mL, 222.5 mg / mL, 225 mg / mL, 227.5 mg / mL, 230 mg / mL, 232.5 mg / mL, 235 mg / mL, 237.5 mg / mL, 240 mg / mL, 242.5 mg / mL, 245 mg / mL, 247.5 mg / mL, or 250 mg / mL.

307. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is at most 18 years old at first loading dose.

308. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is at least 2 years old.

309. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is at least 6 months old.

310. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is from 6 months to 1 year old, or from 1 to 18, from 2 to 18, from 3 to 18, from 4 to 18, from 5 to 18, from 6 to 18, from 7 to 18, from 8 to 18, from 9 to 18, from 10 to 18, from 11 to 18, from 12 to 18, from 13 to 18, from 14 to 18, from 15 to 18, from 16 to 18, or from 17 to 18 years old.WSGR Ref. No.: 47991-748.601311. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is a human from 6 months to 1 year old, or from 1 to 17, from 1 to 16, from 1 to 15, from 1 to 14, from 1 to 13, from 1 to 12, from 1 to 11, from 1 to 10, from 1 to 9, from 1 to 8, from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 1 to 3, or from 1 to 2 years old.

312. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is from 2 to 12 years old.

313. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is from 13 to 18 years old.

314. The method of any one of claims 1, 2, 10-209, and 216-306 or the dosing regimen of any one ofclaims 3-153 and 210-306, wherein the human subject is at least 13 years old.

315. The method of any one of claims 1, 2, 10-209, and 216-314 or the dosing regimen of any one ofclaims 3-153 and 210-314, wherein the race of the human subject is white.

316. The method of any one of claims 1, 2, 10-209, and 216-314 or the dosing regimen of any one ofclaims 3-153 and 210-314, wherein the race of the human subject is Asian.

317. The method of any one of claims 1, 2, 10-209, and 216-314 or the dosing regimen of any one ofclaims 3-153 and 210-314, wherein the race of the human subject is black or African American318. The method of any one of claims 1, 2, 10-209, and 216-314 or the dosing regimen of any one ofclaims 3-153 and 210-314, wherein the human subject receives administration of at least one concomitant anti-seizure medication.

319. The method of any one of claims 1, 2, 10-209, and 216-314 or the dosing regimen of any one ofclaims 3-153 and 210-314, wherein the human subject receives administration of at least 3 or 4 concomitant anti-seizure medications.

320. The method or dosing regimen of claim 318 or 319, wherein the human subject receivesadministration of fenfluramine.

321. The method of any one of claims 1, 2, 10-209, and 216-320 or the dosing regimen of any one ofclaims 3-153 and 210-320, wherein the disease or condition is treated.

322. The method of claim 321, wherein the disease or condition is Dravet Syndrome.

323. The method of claim 321, wherein the disease or condition is SMEB, GEFS+, a Febrile seizure (e.g.,Febrile seizures, familial, 3A), autism, a migraine (e.g., migraine, familial hemiplegic, 3), Alzheimer’s disease, SCN2A encephalopathy, or SCN5A arrhythmia.

324. The method of any one of claims 1, 2, 10-209, and 216-322 or the dosing regimen of any one ofclaims 3-153 and 210-322, wherein the subject is characterized by having: (i) seizure onset prior to 12 months of age with recurrent focal motor or hemiconvulsive orgeneralized tonic-clonic seizures, which are often prolonged and triggered by hyperthermia; (ii) no past history of causal magnetic resonance imaging lesion;(iii) no other known etiology of any diseases or conditions except Dravet Syndrome;(iv) normal development at seizure onset;WSGR Ref. No.: 47991-748.601 (v) a pathogenic variant, or variant of uncertain significance in an SCN1A gene;(vi) at least 2 prior treatments for epilepsy that either had lack of adequate seizure control;(vii) 4 or more convulsive seizures during the 28 days prior to administering, wherein theconvulsive seizures are any one selected from Hemiclonic, Focal with Motor Signs, Focal to Bilateral Tonic Clonic Convulsion, Generalized Tonic Clonic Convulsion, Tonic, Tonic or Atonic (Drop Attacks), and Clonic; (viii) a current intervention for epilepsy or medication with at least one antiepileptic drug at a dosewhich has been stable for at least 4 weeks, wherein the intervention for epilepsy is a ketogenic diet, a vagal nerve stimulator, or a cannabinoid or marijuana-derived product; or (ix) any combination of (i) – (viii).

325. The method of any one of claims 1, 2, 10-209, and 216-323 or the dosing regimen of any one ofclaims 3-153 and 210-323, wherein the subject is additionally characterized by not having one or more of the following: (i) one of the following mutations in the SCN1A gene: Thr226Met, Leu263Val, Val422Leu,Thr1174Ser, Trp1204Arg, Pro1345Ser, Gln1489Lys, Phe1499Leu, Arg1575Cys, Val1611Phe, Leu1624Pro, Arg1648Cys, Leu1649Gln, Leu1670Trp, Gly1674Arg, and Asp1866Tyr; (ii) a known pathogenic mutation in another gene that causes epilepsy, wherein the pathogenicmutation is homozygous in cases of known recessive disease; (iii) currently treated with a sodium channel blocker as maintenance treatment and ananticoagulant, wherein the sodium channel blocker is phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide, and wherein the anticoagulant is not an aspirin; (iv) clinically, significantly unstable medical conditions other than epilepsy;(v) clinically, relevant symptoms or a clinically significant illness in the 4 weeks prior toadministering, other than epilepsy; (vi) a history of brain or spinal cord disease other than epilepsy, Dravet Syndrome or a history ofbacterial meningitis or brain malformation; (vii) a spinal deformity or other condition that alters the free flow of cerebrospinal fluid (CSF) orhaving an implanted CSF drainage shunt; (viii) clinically significant abnormal laboratory values prior to administering;(ix) aspartate aminotransferase or alanine aminotransferase >2.5-fold upper limit of normal,serum creatinine greater than an upper limit of normal or platelet count less than a lower limit of normal; (x) clinically relevant abnormalities in the 12-lead electrocardiogram (ECG) measured at prior toadministering; (xi) a psychiatric or behavioral disorder;WSGR Ref. No.: 47991-748.601 (xii) currently or in the past 4 weeks, medication of an anticoagulant, wherein the anticoagulant isnot aspirin; or (xiii) any combination of (i) – (xiii).

326. The method of any one of claims 1, 2, 10-209, and 216-325 or the dosing regimen of any one ofclaims 3-153 and 210-325, wherein the human subject comprises a deletion, a truncation, a missense, or a nonsense mutation in SCN1A gene.

327. The method of any one of claims 1, 2, 10-209, and 216-326 or the dosing regimen of any one ofclaims 3-153 and 210-326, wherein at least one symptom of Dravet Syndrome in the human subject is reduced or ameliorated.

328. The method or the dosing regimen of claim 327, wherein the symptom of Dravet Syndrome is aseizure.

329. The method of any one of claims 1, 2, 10-209, and 216-328 or the dosing regimen of any one ofclaims 3-153 and 210-328, wherein the method or the dosing regimen reduces or ameliorates seizure frequency, seizure intensity, and / or seizure duration.

330. The method or dosing regimen of claim 329, wherein the reduction or amelioration of seizurefrequency, seizure intensity, and / or seizure duration is sustained for at least 6 months, 9 months, 12 months, 15 months, 18 months, 24 months, 2.5 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 12 years, 14 years, 16 years, 18 years, or longer.

331. The method of any one of claims 1, 2, 10-209, and 216-328 or the dosing regimen of any one ofclaims 3-153 and 210-328, wherein the method or the dosing regimen results in an improvement in a non-seizure-related aspect.

332. The method or dosing regimen of claim 331, wherein the improvement in the non-seizure-relatedaspect is sustained for at least 6 months, 8 months, 12 months, 15 months, 18 months, 24 months, 2.5 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 12 years, 14 years, 16 years, 18 years, or longer.

333. The method or the dosing regimen of claim 331 or 332, wherein the non-seizure-related aspectcomprises a cognitive or behavioral domain selected from the group consisting of communication, daily living skills, socialization and motor skills, and / or wherein the non-seizure-related aspect comprises a cognitive or behavioral subdomain selected from the group consisting of receptive communication, expressive communication, writing skills, personal skills, domestic skills, community skills, interpersonal relationships, play and leisure, coping skills, gross motor skills, and fine motor skills.

334. The method or the dosing regimen of claim 333, wherein the cognitive or behavioral aspect isdetermined according to a standardized assessment.

335. The method or the dosing regimen of claim 334, wherein the standardized assessment comprises aVineland Adaptive Behavior Scale, Third Edition (VABS-III); a Clinical Global Impression of Change (CGI-C); or a Caregiver Global Impression of Change (CaGI-C); or any combination thereof.WSGR Ref. No.: 47991-748.601336. The method or the dosing regimen of claim 334 or 335, wherein (i) the standardized assessmentcomprises VABS-III and the improvement is a positive change in a Gross Scale Value (GSV); (ii) the standardized assessment comprises CGI-C and the improvement is a CGI-C score of 3, 2, or 1; or (iii) the standardized assessment comprises CaGI-C and the improvement is a CaGI-C score of 3, 2, or 1.

337. The method or the dosing regimen of claim 336, wherein the standardized assessment comprisesVABS-III and the positive change in GSV is at least 0.7000, 0.8000, 0.9000, 1.000, 1.250, 1.500, 1.750, 2.000, 2.250, 2.500, 2.750, 3.000, 3.250, 3.500, 3.750, 4.000, 4.250, 4.500, 4.750, 5.000, 5.250, 5.500, 5.750, 6.000, 7.000, 8.000, or 9.000.

338. The method or the dosing regimen of claim 336, wherein the standardized assessment comprisesCGI-C and the improvement is a CGI-C score of 2 or 1.

339. The method or the dosing regimen of claim 336, wherein the standardized assessment comprisesCaGI-C and the improvement is a CaGI-C score of 2 or 1.

340. The method of any one of claims 1, 2, 10-209, and 216-339 or the dosing regimen of any one ofclaims 3-153 and 210-339, wherein the administration (a) reduces or ameliorates seizure frequency, seizure intensity, and / or seizure duration; and (b) results in an improvement in a non-seizure-related aspect.

341. The method of any one of claims 1, 2, 10-209, and 216-340 or the dosing regimen of any one ofclaims 3-153 and 210-340, wherein the method or the dosing regimen results in no treatment- emergent serious adverse event (TESAE) in the human subject related to the administration of the compound of formula (I) or a salt thereof.

342. The method of any one of claims 1, 2, 10-209, and 216-341 or the dosing regimen of any one ofclaims 3-153 and 210-341, further comprising assessing tolerability or effectiveness of the pharmaceutical composition.

343. The method of any one of claims 1, 2, 10-209, and 216-342 or the dosing regimen of any one ofclaims 3-153 and 210-342, further comprising administrating at least one additional therapeutic agent or therapy.

344. The method or the dosing regimen of claim 343, wherein the at least one additional therapeutic agentor therapy is administered at the same time as the first loading dose, the second loading dose and / or the third loading dose.

345. The method or the dosing regimen of claim 343, wherein the at least one additional therapeutic agentor therapy is administered at the same time as the first maintenance dose and / or the one or more further maintenance doses.

346. The method or the dosing regimen of claim 343, wherein the at least one additional therapeutic agentor therapy is administered prior to administration of the first loading dose.

347. The method or the dosing regimen of claim 343, wherein the at least one additional therapeutic agentor therapy is administered after administration of the first loading dose.WSGR Ref. No.: 47991-748.601348. The method or the dosing regimen of any one of claims 343-347, wherein the at least one additionaltherapeutic agent or therapy comprises fenfluramine.

349. The method of any one of claims 1, 2, 10-209, and 216-348 or the dosing regimen of any one ofclaims 3-153 and 210-348, wherein a predicted brain concentration of the compound in the subject after administration of the pharmaceutical composition is at least 1, 2, 4, 6, 8, or 10 µg / mL.

350. The method of any one of claims 1, 10-209, and 216-349 or the dosing regimen of any one of claims3, 6-153 and 210-349, wherein the compound in the mean brain without thalamus of the subject is maintained at a concentration between 5 µg / g and 40 µg / g following intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof and intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof.

351. The method of any one of claims 2, 10-209, and 216-349 or the dosing regimen of any one of claims4-153 and 210-349, wherein the compound in the mean brain without thalamus of the subject is maintained at a concentration between 5 µg / g and 40 µg / g following intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the third loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, and intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.

352. The method of any one of claims 1, 10-209, and 216-349 or the dosing regimen of any one of claims3, 6-153 and 210-349, wherein the compound in the mean brain without thalamus of the subject is maintained at a concentration within the range of about 20% to 140% of about 26 µg / g after intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof and intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof.

353. The method of any one of claims 2, 10-209, and 216-349 or the dosing regimen of any one of claims4-153 and 210-349, wherein the compound in the mean brain without thalamus of the subject is maintained at a concentration within the range of about 20% to 140% of about 26 µg / g after intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the third loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, and intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.

354. The method of any one of claims 1, 2, 10-209, and 216-349 or the dosing regimen of any one ofclaims 3-153 and 210-349, wherein after intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, the compound of formula (I) or a salt thereof formulated in the pharmaceutical composition provides a maximum brain without thalamus concentration within the range of about 80% to 125% of about 26 µg / g followingWSGR Ref. No.: 47991-748.601 intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof.

355. The method of any one of claims 1, 10-209, and 216-349 or the dosing regimen of any one of claims3, 6-153 and 210-349, wherein after intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof and intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, the compound of formula (I) or a salt thereof formulated in the pharmaceutical composition provides a maximum brain without thalamus concentration within the range of about 80% to 125% of about 26 µg / g following intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.

356. The method of any one of claims 2, 10-209, and 216-349 or the dosing regimen of any one of claims4-153 and 210-349, wherein after intrathecal administration of the first loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, intrathecal administration of the second loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, and intrathecal administration of the third loading dose comprising 70 mg of the compound of formula (I) or a salt thereof, the compound of formula (I) or a salt thereof formulated in the pharmaceutical composition provides a maximum brain without thalamus concentration within the range of about 80% to 125% of about 26 µg / g following intrathecal administration of the first maintenance dose comprising 70 mg of the compound of formula (I) or a salt thereof.WSGR Ref. No.: 47991-748.601357. A method of improving a non-seizure-related aspect in a human subject in need thereof, the methodcomprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, thereby improving a non-seizure-related aspect in the human subject, wherein the non-seizure-related aspect comprises a cognitive or behavioral domain selected from the group consisting of communication, daily living skills, socialization and motor skills, and / or wherein the non-seizure-related aspect comprises a cognitive or behavioral subdomain selected from the group consisting of receptive communication, expressive communication, writing skills, personal skills, domestic skills, community skills, interpersonal relationships, play and leisure, coping skills, gross motor skills, and fine motor skills; wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses independently contains the compound at an amount of from about 25 mg to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, and a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the second loading dose, and wherein each maintenance dose after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601358. A method of improving a non-seizure-related aspect in a human subject in need thereof, the methodcomprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, thereby improving a non-seizure-related aspect in the human subject, wherein the non-seizure-related aspect comprises a cognitive or behavioral domain selected from the group consisting of communication, daily living skills, socialization and motor skills, and / or wherein the non-seizure-related aspect comprises a cognitive or behavioral subdomain selected from the group consisting of receptive communication, expressive communication, writing skills, personal skills, domestic skills, community skills, interpersonal relationships, play and leisure, coping skills, gross motor skills, and fine motor skills; wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each dose of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses independently contains the compound at an amount of from about 25 to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, the third loading dose is administered from 2 weeks to 12 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the third loading dose, and wherein each maintenance after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.WSGR Ref. No.: 47991-748.601359. The method of claim 357 or 358, wherein the cognitive or behavioral aspect is determined accordingto a standardized assessment.

360. The method of claim 359, wherein the standardized assessment comprises a Vineland AdaptiveBehavior Scale, Third Edition (VABS-III); a Clinical Global Impression of Change (CGI-C); or a Caregiver Global Impression of Change (CaGI-C); or any combination thereof.

361. The method of claim 359 or 360, wherein (i) the standardized assessment comprises VABS-III andthe improvement is a positive change in a Gross Scale Value (GSV); (ii) the standardized assessment comprises CGI-C and the improvement is a CGI-C score of 3, 2, or 1; or (iii) standardized assessment comprises CaGI-C and the improvement is a CaGI-C score of 3, 2, or 1.

362. The method of claim 361, wherein the standardized assessment comprises VABS-III and thepositive change in GSV is at least 0.7000, 0.8000, 0.9000, 1.000, 1.250, 1.500, 1.750, 2.000, 2.250, 2.500, 2.750, 3.000, 3.250, 3.500, 3.750, 4.000, 4.250, 4.500, 4.750, 5.000, 5.250, 5.500, 5.750, 6.000, 7.000, 8.000, or 9.000.

363. The method of claim 361, wherein the standardized assessment comprises CGI-C and theimprovement is a CGI-C score of 2 or 1.

364. The method of claim 361, wherein the standardized assessment comprises CaGI-C and theimprovement is a CaGI-C score of 2 or 1.

365. A method of reducing seizure frequency, seizure intensity, and / or seizure duration in a humansubject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:WSGR Ref. No.: 47991-748.601 (I), or a salt thereof, thereby reducing seizure frequency, seizure intensity, and / or seizure duration in the human subject, wherein the multiple doses comprise a first loading dose, a second loading dose, and one or more maintenance doses following the second loading dose, wherein each dose of the first loading dose, the second loading dose, and the one or more maintenance doses independently contains the compound at an amount of from about 25 mg to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, and a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the second loading dose, and wherein each maintenance dose after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.

366. A method of reducing seizure frequency, seizure intensity, and / or seizure duration in a humansubject in need thereof, the method comprising administering to the human subject multiple doses of a pharmaceutical composition comprising a compound according to the following chemical structure:(I), or a salt thereof, thereby reducing seizure frequency, seizure intensity, and / or seizure duration in the human subject, wherein the multiple doses comprise a first loading dose, a second loading dose, a third loading dose, and one or more maintenance doses following the third loading dose, wherein each doseWSGR Ref. No.: 47991-748.601 of the first loading dose, the second loading dose, the third loading dose, and the one or more maintenance doses independently contains the compound at an amount of from about 25 mg to about 100 mg, wherein the second loading dose is administered from 4 weeks to 12 weeks after the first loading dose, the third loading dose is administered from 2 weeks to 12 weeks after the second loading dose, a first maintenance dose of the one or more maintenance doses is administered from 8 weeks to 12 months after the third loading dose, and wherein each maintenance after the first maintenance dose is administered independently from 8 weeks to 12 months after the maintenance dose immediately preceding the respective maintenance dose.

367. A method of treating or reducing the likelihood of developing a disease or condition characterizedby a reduced expression or function of NaV1.1 protein in a human subject in need thereof, the method comprising: (1) obtaining a pharmaceutical composition that is a liquid composition comprising a compound in a diluent, wherein the compound is according to the following chemical structure:(I), or a salt thereof, and (2) administering to the human subject multiple doses of the pharmaceutical composition, wherein the multiple doses comprise a first loading dose, a second loading dose, a first maintenance dose following the second loading dose, and one or more maintenance doses following the first maintenance dose, wherein each dose of the first loading dose and the second loading dose contains the compound at an amount of about 70 mg, wherein the firstWSGR Ref. No.: 47991-748.601 maintenance dose and each dose of the one or more maintenance doses contains the compound at an amount of about 45 mg, wherein the second loading dose is administered about 8 weeks after the first loading dose, the first maintenance dose of the one or more maintenance doses is administered about 16 weeks after the second loading dose, and each maintenance dose after the first maintenance dose is administered independently about 16 weeks after a dose immediately preceding the respective maintenance dose.

368. The method of claim 367, wherein diluent comprises:(a) calcium chloride (CaCl2) or calcium chloride dihydrate (CaCl2·2H2O) at a concentration ofabout 0.1 mM to about 50 mM; (b) magnesium chloride (MgCl2) or magnesium chloride hexahydrate (MgCl2·6H2O) at aconcentration of about 0.1 mM to about 50 mM; (c) potassium chloride (KCl) at a concentration of about 0.1 mM to about 20 mM;(d) sodium chloride (NaCl) at a concentration of about 25 mM to about 250 mM; and(e) water.

369. The method of claim 367 or 368, wherein the obtaining comprises diluting a concentrate up to oneweek prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof.

370. The method of claim 367 or 368, wherein the obtaining comprises diluting a concentrate up to 3days prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof.

371. The method of claim 367 or 368, wherein the obtaining comprises diluting a concentrate up to 2days prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof.

372. The method of claim 367 or 368, wherein the obtaining comprises diluting a concentrate up to 24hours prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof.

373. The method of claim 367 or 368, wherein the obtaining comprises diluting a concentrate up to 5hours prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof.

374. The method of claim 367 or 368, wherein the obtaining comprises diluting a concentrate up to onehour prior to the administering the pharmaceutical composition to the human subject, and wherein the concentrate comprises the compound or a salt thereof.

375. The method of any one of claims 367-374, wherein the obtaining comprises diluting the concentratewith the diluent.

376. The method of any one of claims 367-375, wherein the concentrate comprises the compound or asalt thereof dissolved in the diluent.WSGR Ref. No.: 47991-748.601377. The method of any one of claims 367-376, wherein the compound has the following structure:(II).

378. The method of claim 375, wherein the pharmaceutical composition comprises the compound or asalt thereof at a concentration of about 3 mg / mL, about 4.5 mg / mL or about 7 mg / mL.

379. The method of claim 378, wherein the concentrate comprises the compound or a salt thereof at aconcentration of from about 20 mg / mL to about 200 mg / mL, from about 30 mg / mL to about 150 mg / mL, from about 40 mg / mL to about 120 mg / mL, from about 50 mg / mL to about 100 mg / mL, or from about 60 mg / mL to about 80 mg / mL.

380. The method of claim 378, wherein the concentrate comprises the compound or a salt thereof at aconcentration of about 33 mg / mL, about 45 mg / mL, or about 70 mg / mL.

381. The method of any one of claims 367-380, wherein the diluent lacks sodium phosphate.

382. The method of any one of claims 367-381, wherein the diluent comprises 1-2 mM CaCl2 orCaCl2·2H2O.

383. The method of any one of claims 367-381, wherein the diluent comprises about 1.4 mM CaCl2 orCaCl2·2H2O.

384. The method of any one of claims 367-383, wherein the diluent comprises 0.5-1.5 mM MgCl2 orMgCl2·6H2O.

385. The method of any one of claims 367-383, wherein the diluent comprises about 0.79 mM MgCl2 orMgCl2·6H2O.

386. The method of any one of claims 367-385, wherein the diluent comprises from about 1 mM to about2 mM calcium chloride dihydrate.WSGR Ref. No.: 47991-748.601387. The method of any one of claims 367-385, wherein the diluent comprises about 1.4 mM calciumchloride dihydrate.

388. The method of any one of claims 367-387, wherein the diluent comprises from about 0.6 mM toabout 1 mM magnesium chloride hexahydrate.

389. The method of any one of claims 367-387, wherein the diluent comprises about 0.79 mMmagnesium chloride hexahydrate.

390. The method of any one of claims 367-389, wherein the diluent comprises from about 2 mM to about5 mM potassium chloride.

391. The method of any one of claims 367-389, wherein the diluent comprises about 3 mM potassiumchloride.

392. The method of any one of claims 367-391, wherein the diluent comprises from about 125 mM to145 mM sodium chloride.

393. The method of any one of claims 367-391, wherein the diluent comprises about 130 mM sodiumchloride.

394. The method of any one of claims 367-391, wherein the diluent comprises from about 140 mM to160 mM sodium chloride.

395. The method of any one of claims 367-391, wherein the diluent comprises about 150 mM sodiumchloride.

396. The method of any one of claims 367-395, wherein in the pharmaceutical composition:(i) the concentration of the compound is about 3 mg / mL, about 4.5 mg / mL or about 7 mg / mL;(ii) the concentration of calcium chloride dihydrate is about 1.4 mM;(iii) the concentration of magnesium chloride hexahydrate is about 0.79 mM;(iv) the concentration of potassium chloride is about 3 mM; and(v) the concentration of sodium chloride is about 150 mM.

397. The method of any one of claims 367-395, wherein the pharmaceutical composition comprises:(a) calcium ion (Ca2+) at a concentration of about 1.4 mM; (b) magnesium ion (Mg2+) at a concentration of about 0.79 mM; (c) potassium ion (K+) at a concentration of about 3 mM; (d) sodium ion (Na+) at a concentration of about 160 mM; (e) chloride ion (Cl-) at a concentration of about 160 mM; and (f) water.

398. The method of claim 378, wherein in the pharmaceutical composition:(i) the concentration of the compound is about 3 mg / mL, about 4.5 mg / mL or about 7 mg / mL;(ii) the concentration of calcium chloride dihydrate is about 1.4 mM;(iii) the concentration of magnesium chloride hexahydrate is about 0.79 mM;(iv) the concentration of potassium chloride is about 3 mM; and(v) the concentration of sodium chloride is about 150 mM.WSGR Ref. No.: 47991-748.601399. The method of claim 378, wherein the pharmaceutical composition comprises:(a) calcium ion (Ca2+) at a concentration of about 1.4 mM; (b) magnesium ion (Mg2+) at a concentration of about 0.79 mM; (c) potassium ion (K+) at a concentration of about 3 mM; (d) sodium ion (Na+) at a concentration of about 160 mM; (e) chloride ion (Cl-) at a concentration of about 160 mM; and (f) water.

400. The method of any one of claims 367-399, wherein the pharmaceutical composition lacks Na2HPO4and / or NaH2PO4.

401. The method of any one of claims 367-399, wherein the pharmaceutical composition lacks phosphateion.

402. The method of any one of claims 367-401, wherein each dose of the pharmaceutical compositioncomprises 10 mL of the diluent.

403. The method of any one of claims 367-402, wherein the pharmaceutical composition is administeredas a bolus injection.

404. The method of any one of claims 367-403, wherein the method or the dosing regimen comprisesadministering the pharmaceutical composition as a bolus injection over 1 to 60 minutes, 1 to 50 minutes, 1 to 40 minutes, 1 to 30 minutes, 1 to 20 minutes, 1 to 10 minutes, 1 to 5 minutes, or 1 to 3 minutes.

405. The method of any one of claims 367-404, wherein the pharmaceutical composition is administeredby infusion with a delivery pump.

406. The method of any one of claims 367-405, wherein the pharmaceutical composition is administeredby intrathecal injection.

407. The method or dosing regimen of claim 406, wherein each dose of the pharmaceutical compositioncomprises a diluent of a volume of 10 mL, and the diluent is a solution that lacks sodium phosphate.

408. The method of any one of claims 367-407, wherein the pharmaceutical composition does notcomprise a preservative.

409. The method of any one of claims 367-408, wherein the human subject is at most 18 years old at thefirst loading dose.

410. The method of any one of claims 367-408, wherein the human subject is at least 2 years old at thefirst loading dose.

411. The method of any one of claims 367-408, wherein the human subject is at least 6 months old at thefirst loading dose.

412. The method of any one of claims 367-408, wherein the human subject is from 6 months to 1 yearold, or from 1 to 18, from 2 to 18, from 3 to 18, from 4 to 18, from 5 to 18, from 6 to 18, from 7 to 18, from 8 to 18, from 9 to 18, from 10 to 18, from 11 to 18, from 12 to 18, from 13 to 18, from 14 to 18, from 15 to 18, from 16 to 18, or from 17 to 18 years old at the first loading dose.WSGR Ref. No.: 47991-748.601413. The method of any one of claims 367-404, wherein the human subject is a human from 6 months to1 year old, or from 1 to 17, from 1 to 16, from 1 to 15, from 1 to 14, from 1 to 13, from 1 to 12, from 1 to 11, from 1 to 10, from 1 to 9, from 1 to 8, from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 1 to 3, or from 1 to 2 years old at the first loading dose.

414. The method of any one of claims 367-408, wherein the human subject is from 2 to 12 years old atthe first loading dose.

415. The method of any one of claims 367-408, wherein the human subject is from 13 to 18 years old atthe first loading dose.

416. The method of any one of claims 367-408, wherein the human subject is at least 13 years old at thefirst loading dose.

417. The method of any one of claims 367-416, wherein the race of the human subject is white.

418. The method of any one of claims 367-416, wherein the race of the human subject is Asian.

419. The method of any one of claims 367-416, wherein the race of the human subject is black or AfricanAmerican.

420. The method of any one of claims 367-419, wherein the human subject receives administration of atleast one concomitant anti-seizure medication.

421. The method of any one of claims 367-419, wherein the human subject receives administration of atleast 3 or 4 concomitant anti-seizure medications.

422. The method or dosing regimen of claim 420 or 421, wherein the human subject receivesadministration of fenfluramine.

423. The method of any one of claims 367-422, wherein the disease or condition is treated.

424. The method of any one of claims 367-423, wherein the disease or condition is Dravet Syndrome.

425. The method of any one of claims 367-424, wherein the subject is characterized by having:(i) seizure onset prior to 12 months of age with recurrent focal motor or hemiconvulsive orgeneralized tonic-clonic seizures, which are often prolonged and triggered by hyperthermia; (ii) no past history of causal magnetic resonance imaging lesion;(iii) no other known etiology of any diseases or conditions except Dravet Syndrome;(iv) normal development at seizure onset;(v) a pathogenic variant, or variant of uncertain significance in an SCN1A gene;(vi) at least 2 prior treatments for epilepsy that either had lack of adequate seizure control;(vii) 4 or more convulsive seizures during the 28 days prior to administering, wherein theconvulsive seizures are any one selected from Hemiclonic, Focal with Motor Signs, Focal to Bilateral Tonic Clonic Convulsion, Generalized Tonic Clonic Convulsion, Tonic, Tonic or Atonic (Drop Attacks), and Clonic; (viii) a current intervention for epilepsy or medication with at least one antiepileptic drug at a dosewhich has been stable for at least 4 weeks, wherein the intervention for epilepsy is a ketogenic diet, a vagal nerve stimulator, or a cannabinoid or marijuana-derived product; or (ix) any combination of (i) – (viii).WSGR Ref. No.: 47991-748.601426. The method of any one of claims 367-425, wherein the subject is additionally characterized by nothaving one or more of the following: (a) one of the following mutations in the SCN1A gene: Thr226Met, Leu263Val, Val422Leu,Thr1174Ser, Trp1204Arg, Pro1345Ser, Gln1489Lys, Phe1499Leu, Arg1575Cys, Val1611Phe, Leu1624Pro, Arg1648Cys, Leu1649Gln, Leu1670Trp, Gly1674Arg, and Asp1866Tyr; (b) a known pathogenic mutation in another gene that causes epilepsy, wherein the pathogenicmutation is homozygous in cases of known recessive disease; (c) currently treated with a sodium channel blocker as maintenance treatment and ananticoagulant, wherein the sodium channel blocker is phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide, and wherein the anticoagulant is not an aspirin; (d) clinically, significantly unstable medical conditions other than epilepsy;(e) clinically, relevant symptoms or a clinically significant illness in the 4 weeks prior toadministering, other than epilepsy; (f) a history of brain or spinal cord disease other than epilepsy, Dravet Syndrome or a history ofbacterial meningitis or brain malformation; (g) a spinal deformity or other condition that alters the free flow of cerebrospinal fluid (CSF) orhaving an implanted CSF drainage shunt; (h) clinically significant abnormal laboratory values prior to administering;(i) aspartate aminotransferase or alanine aminotransferase >2.5-fold upper limit of normal,serum creatinine greater than an upper limit of normal or platelet count less than a lower limit of normal; (j) clinically relevant abnormalities in the 12-lead electrocardiogram (ECG) measured at prior toadministering; (k) a psychiatric or behavioral disorder;(l) currently or in the past 4 weeks, medication of an anticoagulant, wherein the anticoagulant isnot aspirin; or (m) any combination of (a) – (l).

427. The method of any one of claims 367-426, wherein the human subject comprises a deletion, atruncation, a missense, or a nonsense mutation in SCN1A gene.

428. The method of any one of claims 367-427, wherein at least one symptom of Dravet Syndrome in thehuman subject is reduced or ameliorated.

429. The method of claim 428, wherein the symptom of Dravet Syndrome is a seizure.

430. The method of any one of claims 367-429, wherein the method or the dosing regimen reduces orameliorates seizure frequency, seizure intensity, and / or seizure duration.

431. The method of claim 430, wherein the reduction or amelioration of seizure frequency, seizureintensity, and / or seizure duration is sustained for at least 6 months, 9 months, 12 months, 15 months,WSGR Ref. No.: 47991-748.601 18 months, 24 months, 2.5 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 12 years, 14 years, 16 years, 18 years, or longer.

432. The method of any one of claims 367-431, wherein the method or the dosing regimen results in animprovement in a non-seizure-related aspect.

433. The method of claim 432, wherein the improvement in the non-seizure-related aspect is sustained forat least 6 months, 8 months, 12 months, 15 months, 18 months, 24 months, 2.5 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 12 years, 14 years, 16 years, 18 years, or longer.

434. The method of claim 432 or 433, wherein the non-seizure-related aspect comprises a cognitive orbehavioral domain selected from the group consisting of communication, daily living skills, socialization and motor skills, and / or wherein the non-seizure-related aspect comprises a cognitive or behavioral subdomain selected from the group consisting of receptive communication, expressive communication, writing skills, personal skills, domestic skills, community skills, interpersonal relationships, play and leisure, coping skills, gross motor skills, and fine motor skills.

435. The method of claim 434, wherein the cognitive or behavioral aspect is determined according to astandardized assessment.

436. The method of claim 435, wherein the standardized assessment comprises a Vineland AdaptiveBehavior Scale, Third Edition (VABS-III); a Clinical Global Impression of Change (CGI-C); or a Caregiver Global Impression of Change (CaGI-C); or any combination thereof.

437. The method of claim 435 or 436, wherein (i) the standardized assessment comprises VABS-III andthe improvement is a positive change in a Gross Scale Value (GSV); (ii) the standardized assessment comprises CGI-C and the improvement is a CGI-C score of 3, 2, or 1; or (iii) the standardized assessment comprises CaGI-C and the improvement is a CaGI-C score of 3, 2, or 1.

438. The method of claim 435, wherein the standardized assessment comprises VABS-III and thepositive change in GSV is at least 0.7000, 0.8000, 0.9000, 1.000, 1.250, 1.500, 1.750, 2.000, 2.250, 2.500, 2.750, 3.000, 3.250, 3.500, 3.750, 4.000, 4.250, 4.500, 4.750, 5.000, 5.250, 5.500, 5.750, 6.000, 7.000, 8.000, or 9.000.

439. The method of claim 435, wherein the standardized assessment comprises CGI-C and theimprovement is a CGI-C score of 2 or 1.

440. The method of claim 435, wherein the standardized assessment comprises CaGI-C and theimprovement is a CaGI-C score of 2 or 1.

441. The method of any one of claims 367-440, wherein the administration (a) reduces or amelioratesseizure frequency, seizure intensity, and / or seizure duration; and (b) results in an improvement in a non-seizure-related aspect.

442. The method of any one of claims 367-441, wherein the method or the dosing regimen results in notreatment-emergent serious adverse event (TESAE) in the human subject related to the administration of the compound of formula (I) or a salt thereof.WSGR Ref. No.: 47991-748.601443. The method of any one of claims 367-442, further comprising assessing tolerability or effectivenessof the pharmaceutical composition.

444. The method of any one of claims 367-443, further comprising administrating at least one additionaltherapeutic agent or therapy.

445. The method of claim 444, wherein the at least one additional therapeutic agent or therapy isadministered at the same time as the first loading dose, the second loading dose and / or the third loading dose.

446. The method of claim 444, wherein the at least one additional therapeutic agent or therapy isadministered at the same time as the first maintenance dose and / or the one or more further maintenance doses.

447. The method of claim 444, wherein the at least one additional therapeutic agent or therapy isadministered prior to administration of the first loading dose.

448. The method of claim 444, wherein the at least one additional therapeutic agent or therapy isadministered after administration of the first loading dose.

449. The method of any one of claims 444-448, wherein the at least one additional therapeutic agent ortherapy comprises fenfluramine.

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